SURIGAO STATE COLLEGE OF TECHNOLOGY LEARNING MODULE Module 10 THE CELL CYCLE Topics: 10.1. Phases of the Cell Cycle 10.2. Mitosis and Meiosis 10.3. Programmed Cell Death 10.4 Cancer Time Frame: 4 hours Introduction The cell cycle is an ordered series of events involving cell growth and cell division that produces two new daughter cells. Cells on the path to cell division proceed through a series of precisely timed and carefully regulated stages of growth, DNA replication, and division that produces two identical (clone) cells. This module tackles the stages of mitosis, meosis, programmed cell death, how can cancer occurs and the current treatments. Objectives: Illustrate the phases of the cell cycle. State and discuss the stages of mitosis and meosis; Explain the genetics of cancer; and Discuss the new strategies for combating cancer. Pre-test Bio-3 – Cell and Molecular Biology 1 LEARNING MODULE SURIGAO STATE COLLEGE OF TECHNOLOGY Multiple Choice. Encircle the letter of the best answer. 1. A cell is going through meiosis. The sister chromatids are lined up on the metaphase plate. What phase of meiosis is described here? a. Metaphase I c. Metaphase b. Prophase II d. Anaphase I 2. An adult organism has 60 chromosomes or 30 homologous chromosomes. 30 are maternally derived, 30 are paternally derived. How many chromosomes are in each cell after mitosis? a. 60 chromosomes, 30 homologs. b. 120 chromosomes, 60 homologs. c. 30 chromosomes, no homologs. d. 30 chromosomes, 60 homologs 3. An adult organism has 60 chromosomes or 30 homologous pairs of chromosomes. 30 are maternally derived, 30 are paternally derived. How many chromosomes are in each cell after meiosis? a. 30 chromosomes, no homologous chromosomes. b. 60 chromosomes, 30 homologous chromosomes. c. 120 chromosomes, 60 homologous chromosomes. d. 30 chromosomes, 60 homologs 4. Which of the following is mitosis not applicable? a. Repair (of a wound) in multicellular organisms b. Asexual reproduction in unicellular organisms c. Development (e.g., baby in mother's womb) d. Production of gametes 5. Which choice best describes the cell cycle? Cells grow and develop during interphase. Cells reproduce during the a. mitotic phase. b. Cells grow and develop during the mitotic phase. Cells reproduce during interphase. c. The nucleus of a cell divides during interphase. The cytoplasm of a cell divides during the mitotic phase. d. The nucleus of a cell divides during the mitotic phase. The cytoplasm of a cell divides interphase. 6. During which stage of interphase do cells perform their normal cell functions (such as growing and making enzymes to digest your food)? a. S stage c. G2 stage b. Mitosis d. G1stage 7. Which of the following is true of crossing over? a. Segments of DNA are traded between unrelated chromosomes. b. Crossing over occurs more often in male gametes than female gametes. c. Most homologue pairs do not have any crossover events d. Most homologue pairs do not have any crossover events Bio-3 – Cell and Molecular Biology 2 LEARNING MODULE SURIGAO STATE COLLEGE OF TECHNOLOGY 8. Which of the following explains how apoptosis is related to cancer? a. The cues that would trigger apoptosis have failed in cancer cells. b. Cancer cells are formed when necrosis occurs instead of apoptosis. c. Cancer is an example of uncontrolled apoptosis. d. Cancer cells cause excessive apoptosis in surrounding cells to make room for more cancer cell growth. 9. Which of the following scenarios demonstrates apoptosis? a. An immune cell self-destructs once it is no longer needed by the immune system. b. Muscle fibers are signaled to contract and move. c. A severe burn causes skin cells to die. d. All are correct responses 10. Which of the following is true of normal adult cells but NOT cancer cells? a. Division in the presence of external growth signals b. Contact with other cells increases likelihood of division c. Large amount of telomerase present d. Cell death after a finite number of cell divisions Lesson 10.1 Phases of the Cell Cycle The cell cycle has two major phases: interphase and the mitotic phase (Figure 86). During interphase, the cell grows and DNA is replicated. During the mitotic phase, the replicated DNA and cytoplasmic contents are separated, and the cell divides. Figure 86. The Cell Cycle (www2.le.ac.uk) Interphase During interphase, the cell undergoes normal growth processes while also preparing for cell division. In order for a cell to move from interphase into the mitotic phase, many internal and external conditions must be met. The three stages of interphase Bio-3 – Cell and Molecular Biology 3 LEARNING MODULE SURIGAO STATE COLLEGE OF TECHNOLOGY are called G1, S, and G2. G1 Phase (First Gap) The first stage of interphase is called the G1 phase (first gap) because, from a microscopic aspect, little change is visible. However, during the G 1 stage, the cell is quite active at the biochemical level. The cell is accumulating the building blocks of chromosomal DNA and the associated proteins as well as accumulating sufficient energy reserves to complete the task of replicating each chromosome in the nucleus. S Phase (Synthesis of DNA) Throughout interphase, nuclear DNA remains in a semi-condensed chromatin configuration. In the S phase, DNA replication can proceed through the mechanisms that result in the formation of identical pairs of DNA molecules—sister chromatids— that are firmly attached to the centromeric region. The centrosome is duplicated during the S phase. The two centrosomes will give rise to the mitotic spindle, the apparatus that orchestrates the movement of chromosomes during mitosis. At the center of each animal cell, the centrosomes of animal cells are associated with a pair of rod-like objects, the centrioles, which are at right angles to each other. Centrioles help organize cell division. Centrioles are not present in the centrosomes of other eukaryotic species, such as plants and most fungi. G2 Phase (Second Gap) In the G2 phase, the cell replenishes its energy stores and synthesizes proteins necessary for chromosome manipulation. Some cell organelles are duplicated, and the cytoskeleton is dismantled to provide resources for the mitotic phase. There may be additional cell growth during G2. The final preparations for the mitotic phase must be completed before the cell is able to enter the first stage of mitosis. The Mitotic Phase The mitotic phase is a multistep process during which the duplicated chromosomes are aligned, separated, and move into two new, identical daughter cells. The first portion of the mitotic phase is called karyokinesis, or nuclear division. The second portion of the mitotic phase, called cytokinesis, is the physical separation of the cytoplasmic components into the two daughter cells. Karyokinesis (Mitosis) Karyokinesis, also known as mitosis, is divided into a series of phases—prophase, prometaphase, metaphase, anaphase, and telophase—that result in the division of the cell nucleus (Figure 87). Karyokinesis is also called mitosis. Activity No 1. Bio-3 – Cell and Molecular Biology 4 LEARNING MODULE SURIGAO STATE COLLEGE OF TECHNOLOGY Bio-3 – Cell and Molecular Biology 5 LEARNING MODULE SURIGAO STATE COLLEGE OF TECHNOLOGY Lesson 2. Mitosis and Meiosis What is Mitosis? Mitosis is a type of cell division in which one cell (the mother) divides to produce two new cells (the daughters) that are genetically identical to itself. In the context of the cell cycle, mitosis is the part of the division process in which the DNA of the cell's nucleus is split into two equal sets of chromosomes. The great majority of the cell divisions that happen in your body involve mitosis. During development and growth, mitosis populates an organism’s body with cells, and throughout an organism’s life, it replaces old, worn-out cells with new ones. For single-celled eukaryotes like yeast, mitotic divisions are actually a form of reproduction, adding new individuals to the population. In all of these cases, the “goal” of mitosis is to make sure that each daughter cell gets a perfect, full set of chromosomes. Cells with too few or too many chromosomes usually don’t function well: they may not survive, or they may even cause cancer. So, when cells undergo mitosis, they don’t just divide their DNA at random and toss it into piles for the two daughter cells. Instead, they split up their duplicated chromosomes in a carefully organized series of steps. Phases of mitosis Mitosis consists of four basic phases: prophase, metaphase, anaphase, and telophase. Some textbooks list five, breaking prophase into an early phase (called prophase) and a late phase (called prometaphase). These phases occur in strict sequential order, and cytokinesis - the process of dividing the cell contents to make two new cells - starts in anaphase or telophase. Let’s start by looking at a cell right before it begins mitosis. This cell is in interphase (late G_22start subscript, 2, end subscript phase) and has already copied its DNA, Bio-3 – Cell and Molecular Biology 6 LEARNING MODULE SURIGAO STATE COLLEGE OF TECHNOLOGY so the chromosomes in the nucleus each consist of two connected copies, called sister chromatids. You can’t see the chromosomes very clearly at this point, because they are still in their long, stringy, decondensed form. This animal cell has also made a copy of its centrosome, an organelle that will play a key role in orchestrating mitosis, so there are two centrosomes. (Plant cells generally don’t have centrosomes with centrioles, but have a different type of microtubule organizing center that plays a similar role.) Figure 87. Phases of Mitosis (courses.lumenlearning.com) Prophase In early prophase, the cell starts to break down some structures and build others up, setting the stage for division of the chromosomes. The chromosomes start to condense (making them easier to pull apart later on). The mitotic spindle begins to form. The spindle is a structure made of microtubules, strong fibers that are part of the cell’s “skeleton.” Its job is to organize the chromosomes and move them around during mitosis. The spindle grows between the centrosomes as they move apart. The nucleolus (or nucleoli, plural), a part of the nucleus where ribosomes are made, disappears. This is a sign that the nucleus is getting ready to break down. In late prophase (sometimes also called prometaphase), the mitotic spindle begins to capture and organize the chromosomes. The chromosomes become even more condensed, so they are very compact. The nuclear envelope breaks down, releasing the chromosomes. The mitotic spindle grows more, and some of the microtubules start to “capture” Bio-3 – Cell and Molecular Biology 7 LEARNING MODULE SURIGAO STATE COLLEGE OF TECHNOLOGY chromosomes. Microtubules can bind to chromosomes at the kinetochore, a patch of protein found on the centromere of each sister chromatid. (Centromeres are the regions of DNA where the sister chromatids are most tightly connected.) Microtubules that bind a chromosome are called kinetochore microtubules. Microtubules that don’t bind to kinetochores can grab on to microtubules from the opposite pole, stabilizing the spindle. More microtubules extend from each centrosome towards the edge of the cell, forming a structure called the aster. Metaphase Chromosomes line up at the metaphase plate, under tension from the mitotic spindle. The two sister chromatids of each chromosome are captured by microtubules from opposite spindle poles. In metaphase, the spindle has captured all the chromosomes and lined them up at the middle of the cell, ready to divide. All the chromosomes align at the metaphase plate (not a physical structure, just a term for the plane where the chromosomes line up). At this stage, the two kinetochores of each chromosome should be attached to microtubules from opposite spindle poles. Before proceeding to anaphase, the cell will check to make sure that all the chromosomes are at the metaphase plate with their kinetochores correctly attached to microtubules. This is called the spindle checkpoint and helps ensure that the sister chromatids will split evenly between the two daughter cells when they separate in the next step. If a chromosome is not properly aligned or attached, the cell will halt division until the problem is fixed. Anaphase The sister chromatids separate from one another and are pulled towards opposite poles of the cell. The microtubules that are not attached to chromosomes push the two poles of the spindle apart, while the kinetochore microtubules pull the chromosomes towards the poles. In anaphase, the sister chromatids separate from each other and are pulled towards opposite ends of the cell. The protein “glue” that holds the sister chromatids together is broken down, allowing them to separate. Each is now its own chromosome. The chromosomes of each pair are pulled towards opposite ends of the cell. Microtubules not attached to chromosomes elongate and push apart, separating the poles and making the cell longer. All of these processes are driven by motor proteins, molecular machines that can “walk” along microtubule tracks and carry a cargo. In mitosis, motor proteins carry chromosomes or other microtubules as they walk. Telophase The spindle disappears, a nuclear membrane re-forms around each set of chromosomes, and a nucleolus reappears in each new nucleus. The chromosomes Bio-3 – Cell and Molecular Biology 8 LEARNING MODULE SURIGAO STATE COLLEGE OF TECHNOLOGY also start to decondense. In telophase, the cell is nearly done dividing, and it starts to re-establish its normal structures as cytokinesis (division of the cell contents) takes place. The mitotic spindle is broken down into its building blocks. Two new nuclei form, one for each set of chromosomes. Nuclear membranes and nucleoli reappear. The chromosomes begin to decondense and return to their “stringy” form. Cytokinesis in animal and plant cells. Cytokinesis in an animal cell: an actin ring around the middle of the cell pinches inward, creating an indentation called the cleavage furrow. Cytokinesis in a plant cell: the cell plate forms down the middle of the cell, creating a new wall that partitions it in two. Cytokinesis, the division of the cytoplasm to form two new cells, overlaps with the final stages of mitosis. It may start in either anaphase or telophase, depending on the cell, and finishes shortly after telophase. In animal cells, cytokinesis is contractile, pinching the cell in two like a coin purse with a drawstring. The “drawstring” is a band of filaments made of a protein called actin, and the pinch crease is known as the cleavage furrow. Plant cells can’t be divided like this because they have a cell wall and are too stiff. Instead, a structure called the cell plate forms down the middle of the cell, splitting it into two daughter cells separated by a new wall. When division is complete, it produces two daughter cells. Each daughter cell has a complete set of chromosomes, identical to that of its sister (and that of the mother cell). The daughter cells enter the cell cycle in G1. When cytokinesis finishes, we end up with two new cells, each with a complete set of chromosomes identical to those of the mother cell. The daughter cells can now begin their own cellular “lives,” and – depending on what they decide to be when they grow up – may undergo mitosis themselves, repeating the cycle. Activity No. 2 Mitosis - Internet Lesson In this internet lesson, you will review the steps of mitosis and view video simulations of cell division. Mitosis Tutorial http://www.cellsalive.com/ Click on the link to “MITOSIS” Read the text on this page and view the animation, you can slow down the video by clicking step by step through the phases. 1. Which stage does the following occur: Chromatin condenses into chromosomes ___________________________________________ Bio-3 – Cell and Molecular Biology 9 LEARNING MODULE SURIGAO STATE COLLEGE OF TECHNOLOGY Chromosomes align in center ___________________________________________ of cell. Longest part of the cell cycle. ___________________________________________ Nuclear envelope breaks down. ___________________________________________ Cell is cleaved into two new daughter cells. ___________________________________________ Daughter chromosomes arrive at the poles. ___________________________________________ Chromatids are pulled apart ___________________________________________ Watch the video carefully. 2. The colored chromosomes represent chromatids. There are two of each color because one is an exact duplicate of the other. -How many chromosomes are visible at the beginning of mitosis? ________________ -- How many are in each daughter cell at the end of mitosis? __________________ --The little green T shaped things on the cell are: ____________________________ -- What happens to the centrioles during mitosis? _______________________ 3. Identify the stages of mitosis in these cells Bio-3 – Cell and Molecular Biology 10 LEARNING MODULE SURIGAO STATE COLLEGE OF TECHNOLOGY Meiosis Meiosis, also called reduction division, division of a germ cell involving two fissions of the nucleus and giving rise to four gametes, or sex cells, each possessing half the number of chromosomes of the original cell. The process of meiosis is characteristic of organisms that reproduce sexually. Such species have in the nucleus of each cell a diploid (double) set of chromosomes, consisting of two haploid sets (one inherited from each parent). These haploid sets are homologous—i.e., they contain the same kinds of genes, but not necessarily in the same form. In humans, for example, each set of homologous chromosomes contains a gene for blood type, but one set may have the gene for blood type A and the other set the gene for blood type B. To put that another way, meiosis in humans is a division process that takes us from a diploid cell—one with two sets of chromosomes—to haploid cells—ones with a single set of chromosomes. In humans, the haploid cells made in meiosis are sperm and eggs. When a sperm and an egg join in fertilization, the two haploid sets of chromosomes form a complete diploid set: a new genome. Prior to meiosis, each of the chromosomes in the diploid germ cell has replicated and thus consists of a joined pair of duplicate chromatids. Meiosis begins with the contraction of the chromosomes in the nucleus of the diploid cell. Homologous paternal and maternal chromosomes pair up along the midline of the cell. Each pair of chromosomes—called a tetrad, or a bivalent—consists of four chromatids. At this point, the homologous chromosomes exchange genetic material by the process of crossing over. The homologous pairs then separate, each pair being pulled to opposite ends of the cell, which then pinches in half to form two daughter cells. Each daughter cell of this first meiotic division contains a haploid set of chromosomes. The chromosomes at this point still consist of duplicate chromatids. In the second meiotic division, each haploid daughter cell divides. There is no further reduction in chromosome number during this division, as it involves the separation of each chromatid pair into two chromosomes, which are pulled to the opposite ends of the daughter cells. Each daughter cell then divides in half, thereby producing a total of four different haploid gametes. When two gametes unite during fertilization, each contributes its haploid set of chromosomes to the new individual, restoring the diploid number. To put that another way, meiosis in humans is a division process that takes us from a diploid cell—one with two sets of chromosomes—to haploid cells—ones with a single set of chromosomes. In humans, the haploid cells made in meiosis are sperm and eggs. When a sperm and an egg join in fertilization, the two haploid sets of chromosomes form a complete diploid set: a new genome. . Bio-3 – Cell and Molecular Biology 11 LEARNING MODULE SURIGAO STATE COLLEGE OF TECHNOLOGY Figure 88. Phases of Meiosis (courses.lumenlearning.com) Prophase I Prophase I, the first step in meiosis I, is similar to prophase in mitosis in that the chromosomes condense and move towards the middle of the cell. The nuclear envelope degrades, which allows the microtubules originating from the centrioles on either side of the cell to attach to the kinetochores in the centromeres of each chromosome. Unlike in mitosis, the chromosomes pair with their homologous partner. This can be seen in the red and blue chromosomes that pair together in the diagram. This step does not take place in mitosis. At the end of prophase I and the beginning of metaphase I, homologous chromosomes are primed for crossing-over. Between prophase I and metaphase I, homologous chromosomes can swap parts of themselves that house the same genes. This is called crossing-over and is responsible for the other law of genetics, the law of independent assortment. This law states that traits are inherited independently of each other. For traits on different chromosomes, this is certainly true all of the time. For traits on the same chromosome, crossing-over makes it possible for the maternal and paternal DNA to recombine, allowing traits to be inherited in an almost infinite number of ways. Bio-3 – Cell and Molecular Biology 12 LEARNING MODULE SURIGAO STATE COLLEGE OF TECHNOLOGY Metaphase I In metaphase I of meiosis I, the homologous pairs of chromosomes line up on the metaphase plate, near the center of the cell. This step is referred to as a reductional division. The homologous chromosomes that contain the two different alleles for each gene are lined up to be separated. As seen in the diagram above, while the chromosomes line up on the metaphase plate with their homologous pair, there is no order upon which side the maternal or paternal chromosomes line up. This process is the molecular reason behind the law of segregation. The law of segregation tells us that each allele has the same chance of being passed on to offspring. In metaphase I of meiosis, the alleles are separated, allowing for this phenomenon to happen. In meiosis II, they will be separated into individual gametes. In mitosis, all the chromosomes line up on their centromeres, and the sister chromatids of each chromosome separate into new cells. The homologous pairs do not pair up in mitosis, and each is split in half to leave the new cells with 2 different alleles for each gene. Even if these alleles are the same allele, they came from a maternal and paternal source. In meiosis, the lining up of homologous chromosomes leaves 2 alleles in the final cells, but they are on sister chromatids and are clones of the same source of DNA. Anaphase I Much like anaphase of mitosis, the chromosomes are now pulled towards the centrioles at each side of the cell. However, the centrosomes holding the sister chromatids together do not dissolve in anaphase I of meiosis, meaning that only homologous chromosomes are separated, not sister chromatids. Telophase I In telophase I, the chromosomes are pulled completely apart and new nuclear envelopes form. The plasm membrane is separated by cytokinesis and two new cells are effectively formed. Results of Meiosis I Two new cells, each haploid in their DNA, but with 2 copies, are the result of meiosis I. Again, although there are 2 alleles for each gene, they are on sister chromatid copies of each other. These are therefore considered haploid cells. These cells take a short rest before entering the second division of meiosis, meiosis II. Phases of Meiosis II Prophase II Prophase II resembles prophase I. The nuclear envelopes disappear and centrioles are formed. Microtubules extend across the cell to connect to the kinetochores of Bio-3 – Cell and Molecular Biology 13 LEARNING MODULE SURIGAO STATE COLLEGE OF TECHNOLOGY individual chromatids, connected by centromeres. The chromosomes begin to get pulled toward the metaphase plate. Metaphase II Now resembling mitosis, the chromosomes line up with their centromeres on the metaphase plate. One sister chromatid is on each side of the metaphase plate. At this stage, the centromeres are still attached by the protein cohesin. Anaphase II The sister chromatids separate. They are now called sister chromosomes and are pulled toward the centrioles. This separation marks the final division of the DNA. Unlike the first division, this division is known as an equational division, because each cell ends up with the same quantity of chromosomes as when the division started, but with no copies. Telophase II As in the previous telophase I, the cell is now divided into two and the chromosomes are on opposite ends of the cell. Cytokinesis or plasma division occurs, and new nuclear envelopes are formed around the chromosomes. Results of Meiosis II At the end of meiosis II, there are 4 cells, each haploid, and each with only 1 copy of the genome. These cells can now be developed into gametes, eggs in females and sperm in males. Examples of Meiosis Human Meiosis Human meiosis occurs in the sex organs. Male testis produce sperm and female ovaries produce eggs. Before these gametes are made, however, the DNA must be reduced. Humans have 23 distinct chromosomes, existing in homologous pairs between maternal and paternal DNA, meaning 46 chromosomes. Before meiosis, the DNA in the cell is replicated, producing 46 chromosomes in 92 sister chromatids. Each pair of sister chromatids has a corresponding (either maternal or paternal) set of sister chromosomes. These pairs are known as homologous chromosomes. During meiosis I, these homologous chromosomes line up and divide. This leaves 23 chromosomes in each cell, each chromosome consisting of sister chromatids. These chromatids may no longer be identical, as crossing-over may have occurred during metaphase I of meiosis I. Finally, meiosis II takes place, and the sister chromatids are separated into individual cells. This leaves 4 cells, each with 23 chromosomes, or 4 haploid cells. Fruit Flies Bio-3 – Cell and Molecular Biology 14 LEARNING MODULE SURIGAO STATE COLLEGE OF TECHNOLOGY Fruit flies have 4 pairs of chromosomes or 8 chromosomes in regular cells. Before meiosis takes place, each chromosome is replicated, leaving 8 chromosomes and 16 sister chromatids. Meiosis I takes place, and there are 2 cells, each with only 4 chromosomes. Each chromosome is still made of sister chromatids, and some crossing-over may have occurred during metaphase I. Meiosis II now takes place on those two cells. In total, 4 cells are created, again. However, these cells have 4 chromosomes. When two gametes meet to create a new fruit fly, the resulting zygote will have 8 chromosomes of 4 pairs of sister chromosomes, 4 coming from each parent. Activity No. 3 Bio-3 – Cell and Molecular Biology 15 LEARNING MODULE SURIGAO STATE COLLEGE OF TECHNOLOGY Bio-3 – Cell and Molecular Biology 16 LEARNING MODULE SURIGAO STATE COLLEGE OF TECHNOLOGY Lesson 10.3. Programmed Cell Death Programmed cell death (PCD; sometimes referred to as cellular suicide) is the death of a cell as a result of events inside of a cell, such as apoptosis or autophagy. PCD is carried out in a biological process, which usually confers advantage during an organism's life-cycle. You may think of it as a bad thing for cells in your body to die. In many cases, that’s true: it’s not good for cells to die because of an injury (for example, from a scrape or a harmful chemical). However, it’s also important that some cells of our bodies do die – not randomly, but in a carefully controlled way. For example, have you ever wondered how your fingers formed? It turns out that the cells between your developing fingers were instructed to die long ago, while you were still an embryo. If they hadn’t done so, you would have webbed hands, or perhaps just paddles of tissue with no fingers at all. The cells between your embryonic fingers died in a process called apoptosis, a common form of programmed cell death. In programmed cell death, cells undergo “cellular suicide” when they receive certain cues. Apoptosis involves the death of a cell, but it benefits the organism as a whole (for instance, by letting fingers develop or eliminating potential cancer cells). In this article, we’ll take a closer look at apoptosis, seeing when it happens and why it’s important. Apoptosis vs. necrosis Broadly speaking, there are two ways that cells die in a multicellular organism such as yourself: They are killed by things that harm them (such as toxic chemicals or physical injury), a process called necrosis. They are triggered to undergo programmed cell death. The best-understood form of programmed cell death is apoptosis. Necrosis and apoptosis occur under different circumstances and involve different steps. Simply put, necrosis is messy and causes an immune response of Bio-3 – Cell and Molecular Biology 17 LEARNING MODULE SURIGAO STATE COLLEGE OF TECHNOLOGY inflammation, while apoptosis is tidy and splits the cell into little parcels that can be taken up and recycled by other cells (Figure 89). Necrosis (the messy way) When cells are damaged by harmful factors (such as injury or toxic chemicals), they usually “spill their guts” as they die. Because the damaged cell’s plasma membrane can no longer control the passage of ions and water, the cell swells up, and its contents leak out through holes in the plasma membrane. This often causes inflammation in the tissue surrounding the dead cell. Figure 89. Comparison of necrosis and Apoptosis (khanacademy.org) Apoptosis (the tidy way) Cells that undergo apoptosis go through a different and much more orderly process. They shrink and develop bubble-like protrusions (technical name: “blebs”) on their surface. The DNA in the nucleus gets chopped up into small pieces, and some organelles of the cell, such as the endoplasmic reticulum, break down into fragments. In the end, the entire cell splits up into small chunks, each neatly enclosed in a package of membrane. What happens to the chunks? They release signals that attract debris-eating (phagocytic) immune cells, such as macrophages. Also, the fragments of the dying cell display a lipid molecule called phosphatidylserine on their surface. Phosphatidylserine is usually hidden on the inside of the membrane, and when it is on the outside, it lets the phagocytes bind and "eat" the cell fragments. Why do cells undergo apoptosis? Many cells in the human body have the built-in ability to undergo apoptosis (in the Bio-3 – Cell and Molecular Biology 18 LEARNING MODULE SURIGAO STATE COLLEGE OF TECHNOLOGY same way that they have the built-in ability to copy their DNA or break down fuels). Basically, apoptosis is a general and convenient way to remove cells that should no longer be part of the organism. Some cells need to be “deleted” during development – for instance, to whittle an intricate structure like a hand out of a larger block of tissue. Some cells are abnormal and could hurt the rest of the organism if they survive, such as cells with viral infections or DNA damage. Cells in an adult organism may be eliminated to maintain balance – to make way for new cells or remove cells needed only for temporary tasks. Apoptosis is Part of Development In many organisms, programmed cell death is a normal part of development. In some cases, apoptosis during development occurs in a very predictable way: in the worm C. elegans, 131 cells will die by apoptosis as the worm develops from a single cell to an adult (and we know exactly which ones they are) Apoptosis also plays a key role in human development. For instance, as we saw in the introduction, your hand started out as a paddle-like block of tissue when you were an embryo. The block was “carved” into fingers by apoptosis of the cells in between the developing fingers. Figure 90. Developing mouse paw showing apoptosis (khanacademy.org) Microscope images from a scientific paper, showing a developing mouse paw. The cells between the developing digits are stained by a marker that indicates apoptotic cells (Figure 90). This process occurs in all sorts of vertebrate species that have finger- or toe-like digits, and less apoptosis results in more webbing between the digits. Sometimes, if Bio-3 – Cell and Molecular Biology 19 LEARNING MODULE SURIGAO STATE COLLEGE OF TECHNOLOGY a small mistake happens during finger or toe development, apoptosis may be incomplete (leading, for instance, to fused toes). Other examples of apoptosis during normal development include the loss of a tadpole’s tail as it turns into a frog, and the removal of unneeded neurons in as neural circuits in the brain are “wired.” Apoptosis can eliminate infected or cancerous cells In some cases, a cell can pose a threat to the rest of the body if it survives. For instance, this may be the case for cells with DNA damage, pre-cancerous cells, and cells infected by viruses. If these cells undergo apoptosis, the threat to the rest of the organism (such as cancer or spread of a viral infection) is removed. When a cell’s DNA is damaged, it will typically detect the damage and try to repair it. If the damage is beyond repair, the cell will normally send itself into apoptosis, ensuring that it will not pass on its damaged DNA. When cells have DNA damage but fail to undergo apoptosis, they may be on the road to cancer (Figure 91). Figure 91. Apoptosis can remove the threat of producing cancer cells (khanacademy.org) Sometimes, pre-cancerous cells that have avoided internal apoptosis cues are detected by immune cells, which try to trigger apoptosis through an external signaling pathway. Successful cancer cells, however, manage to duck both internal and external cues that would normally trigger apoptosis. This allows them to divide out of control and accumulate mutations (changes in their DNA). Apoptosis is key to immune function Apoptosis also plays an essential role in the development and maintenance of a Bio-3 – Cell and Molecular Biology 20 LEARNING MODULE SURIGAO STATE COLLEGE OF TECHNOLOGY healthy immune system. When B and T cells (immune cells that bind specific molecules) are first produced, they’re tested to see if they react against any of the body’s own “self” components. Cells that do are eliminated right away by apoptosis. If this process fails, self-reactive cells may be released into the body, where they can attack tissues and cause autoimmune conditions. Apoptosis also plays an important role in allowing the immune system to turn off its response to a pathogen. When a pathogen is detected, the immune cells that recognize the pathogen divide extensively, undergoing a huge increase in numbers with the purpose of destroying the pathogen. Once the pathogen is cleared from the body, the large numbers of pathogen-specific immune cells are no longer needed and must be removed by apoptosis to maintain homeostasis (balance) in the immune system. Lesson 10.4 Cancer What is Cancer? Cancer is a broad term. It describes the disease that results when cellular changes cause the uncontrolled growth and division of cells. In all types of cancer, some of the body’s cells begin to divide without stopping and spread into surrounding tissues. Cancer can start almost anywhere in the human body, which is made up of trillions of cells. Normally, human cells grow and divide to form new cells as the body needs them. When cells grow old or become damaged, they die, and new cells take their place. When cancer develops, however, this orderly process breaks down. As cells become more and more abnormal, old or damaged cells survive when they should die, and new cells form when they are not needed. These extra cells can divide without stopping and may form growths called tumors. Many cancers form solid tumors, which are masses of tissue. Cancers of the blood, such as leukemias, generally do not form solid tumors. Cancerous tumors are malignant, which means they can spread into, or invade, nearby tissues. In addition, as these tumors grow, some cancer cells can break off and travel to distant places in the body through the blood or the lymph system and form new tumors far from the original tumor. Unlike malignant tumors, benign tumors do not spread into, or invade, nearby tissues. Benign tumors can sometimes be quite large, however. When removed, they usually don’t grow back, whereas malignant tumors sometimes do. Unlike most benign tumors elsewhere in the body, benign brain tumors can be life threatening. Differences between Cancer Cells and Normal Cells Cancer cells differ from normal cells in many ways that allow them to grow out of control and become invasive. One important difference is that cancer cells are less specialized than normal cells. That is, whereas normal cells mature into very distinct cell types with specific functions, cancer cells do not. This is one reason that, unlike Bio-3 – Cell and Molecular Biology 21 LEARNING MODULE SURIGAO STATE COLLEGE OF TECHNOLOGY normal cells, cancer cells continue to divide without stopping. In addition, cancer cells are able to ignore signals that normally tell cells to stop dividing or that begin a process known as programmed cell death, or apoptosis, which the body uses to get rid of unneeded cells. Cancer cells may be able to influence the normal cells, molecules, and blood vessels that surround and feed a tumor—an area known as the microenvironment. For instance, cancer cells can induce nearby normal cells to form blood vessels that supply tumors with oxygen and nutrients, which they need to grow. These blood vessels also remove waste products from tumors. Cancer cells are also often able to evade the immune system, a network of organs, tissues, and specialized cells that protects the body from infections and other conditions. Although the immune system normally removes damaged or abnormal cells from the body, some cancer cells are able to “hide” from the immune system. Tumors can also use the immune system to stay alive and grow. For example, with the help of certain immune system cells that normally prevent a runaway immune response, cancer cells can actually keep the immune system from killing cancer cells. How Cancer Arises Figure 92. Cancer is caused by certain changes to genes, the basic physical units of inheritance. Genes are arranged in long strands of tightly packed DNA called chromosomes. (Terese Winslow) Bio-3 – Cell and Molecular Biology 22 LEARNING MODULE SURIGAO STATE COLLEGE OF TECHNOLOGY Genetic changes that cause cancer can be inherited from our parents. They can also arise during a person’s lifetime as a result of errors that occur as cells divide or because of damage to DNA caused by certain environmental exposures. Cancercausing environmental exposures include substances, such as the chemicals in tobacco smoke, and radiation, such as ultraviolet rays from the sun. Each person’s cancer has a unique combination of genetic changes. As the cancer continues to grow, additional changes will occur. Even within the same tumor, different cells may have different genetic changes. In general, cancer cells have more genetic changes, such as mutations in DNA (Figure 92), than normal cells. Some of these changes may have nothing to do with the cancer; they may be the result of the cancer, rather than its cause. Fundamentals of Cancer How Does Cancer Form? Figure 93. Cancer Cells (cancer.gov) "Drivers" of Cancer Cancer is a disease caused when cells divide uncontrollably and spread into surrounding tissues The genetic changes that contribute to cancer tend to affect three main types of genes—proto-oncogenes, tumor suppressor genes, and DNA repair genes. These Bio-3 – Cell and Molecular Biology 23 LEARNING MODULE SURIGAO STATE COLLEGE OF TECHNOLOGY changes are sometimes called “drivers” of cancer. Proto-oncogenes are involved in normal cell growth and division. However, when these genes are altered in certain ways or are more active than normal, they may become cancer-causing genes (or oncogenes), allowing cells to grow and survive when they should not. Tumor suppressor genes are also involved in controlling cell growth and division. Cells with certain alterations in tumor suppressor genes may divide in an uncontrolled manner. DNA repair genes are involved in fixing damaged DNA. Cells with mutations in these genes tend to develop additional mutations in other genes. Together, these mutations may cause the cells to become cancerous. As scientists have learned more about the molecular changes that lead to cancer, they have found that certain mutations commonly occur in many types of cancer. Because of this, cancers are sometimes characterized by the types of genetic alterations that are believed to be driving them, not just by where they develop in the body and how the cancer cells look under the microscope. When Cancer Spreads ENLARGE A cancer that has spread from the place where it first started to another place in the body is called metastatic cancer. The process by which cancer cells spread to other parts of the body is called metastasis. Metastatic cancer has the same name and the same type of cancer cells as the original, or primary, cancer. For example, breast cancer that spreads to and forms a metastatic tumor in the lung is metastatic breast cancer, not lung cancer. Under a microscope, metastatic cancer cells generally look the same as cells of the original cancer. Moreover, metastatic cancer cells and cells of the original cancer usually have some molecular features in common, such as the presence of specific chromosome changes. Treatment may help prolong the lives of some people with metastatic cancer. In general, though, the primary goal of treatments for metastatic cancer is to control the growth of the cancer or to relieve symptoms caused by it. Metastatic tumors can cause severe damage to how the body functions, and most people who die of cancer die of metastatic disease. Bio-3 – Cell and Molecular Biology 24 LEARNING MODULE SURIGAO STATE COLLEGE OF TECHNOLOGY Figure 94. Metastasis of cancer cells (cancer.gov) In metastasis, cancer cells break away from where they first formed (primary cancer), travel through the blood or lymph system, and form new tumors (metastatic tumors) in other parts of the body. The metastatic cancer is the same type of cancer as primary tumor. Tissue Changes that Are Not Cancer Not every change in the body’s tissues is cancer. Some tissue changes may develop into cancer if they are not treated, however. Here are some examples of tissue changes that are not cancer but, in some cases, are monitored: Hyperplasia occurs when cells within a tissue divide faster than normal and extra cells build up, or proliferate. However, the cells and the way the tissue is organized look normal under a microscope. Hyperplasia can be caused by several factors or conditions, including chronic irritation. Dysplasia is a more serious condition than hyperplasia. In dysplasia, there is also a buildup of extra cells. But the cells look abnormal and there are changes in how the tissue is organized. In general, the more abnormal the cells and tissue look, the greater the chance that cancer will form. Some types of dysplasia may need to be monitored or treated. An example of dysplasia is an abnormal mole (called a dysplastic nevus) that forms on the skin. A dysplastic nevus can turn into melanoma, although most do not. An even more serious condition is carcinoma in situ. Although it is sometimes called cancer, carcinoma in situ is not cancer because the abnormal cells do not spread beyond the original tissue. That is, they do not invade nearby tissue the way that Bio-3 – Cell and Molecular Biology 25 LEARNING MODULE SURIGAO STATE COLLEGE OF TECHNOLOGY cancer cells do. But, because some carcinomas in situ may become cancer, they are usually treated. Figure 95. Comparison of Normal cells, hyperplasia, dysplasia and cancer cells (cancer.gov) Normal cells may become cancer cells. Before cancer cells form in tissues of the body, the cells go through abnormal changes called hyperplasia and dysplasia. In hyperplasia, there is an increase in the number of cells in an organ or tissue that appear normal under a microscope. In dysplasia, the cells look abnormal under a microscope but are not cancer. Hyperplasia and dysplasia may or may not become cancer (Figure 95). Types of Cancer There are more than 100 types of cancer. Types of cancer are usually named for the organs or tissues where the cancers form. For example, lung cancer starts in cells of the lung, and brain cancer starts in cells of the brain. Cancers also may be described by the type of cell that formed them, such as an epithelial cell or a squamous cell. Here are some categories of cancers that begin in specific types of cells: Carcinoma Carcinomas are the most common type of cancer. They are formed by epithelial cells, which are the cells that cover the inside and outside surfaces of the body. There are many types of epithelial cells, which often have a column-like shape when viewed under a microscope. Carcinomas that begin in different epithelial cell types have specific names: Adenocarcinoma is a cancer that forms in epithelial cells that produce fluids or mucus. Tissues with this type of epithelial cell are sometimes called glandular tissues. Most cancers of the breast, colon, and prostate are adenocarcinomas. Basal cell carcinoma is a cancer that begins in the lower or basal (base) layer of the epidermis, which is a person’s outer layer of skin. Bio-3 – Cell and Molecular Biology 26 LEARNING MODULE SURIGAO STATE COLLEGE OF TECHNOLOGY Squamous cell carcinoma is a cancer that forms in squamous cells, which are epithelial cells that lie just beneath the outer surface of the skin. Squamous cells also line many other organs, including the stomach, intestines, lungs, bladder, and kidneys. Squamous cells look flat, like fish scales, when viewed under a microscope. Squamous cell carcinomas are sometimes called epidermoid carcinomas. Transitional cell carcinoma is a cancer that forms in a type of epithelial tissue called transitional epithelium, or urothelium. This tissue, which is made up of many layers of epithelial cells that can get bigger and smaller, is found in the linings of the bladder, ureters, and part of the kidneys (renal pelvis), and a few other organs. Some cancers of the bladder, ureters, and kidneys are transitional cell carcinomas. Sarcoma Sarcomas are cancers that form in bone and soft tissues, including muscle, fat, blood vessels, lymph vessels, and fibrous tissue (such as tendons and ligaments). Osteosarcoma is the most common cancer of bone. The most common types of soft tissue sarcoma are leiomyosarcoma, Kaposi sarcoma, malignant fibrous histiocytoma, liposarcoma, and dermatofibrosarcoma protuberans. Leukemia Cancers that begin in the blood-forming tissue of the bone marrow are called leukemias. These cancers do not form solid tumors. Instead, large numbers of abnormal white blood cells (leukemia cells and leukemic blast cells) build up in the blood and bone marrow, crowding out normal blood cells. The low level of normal blood cells can make it harder for the body to get oxygen to its tissues, control bleeding, or fight infections. There are four common types of leukemia, which are grouped based on how quickly the disease gets worse (acute or chronic) and on the type of blood cell the cancer starts in (lymphoblastic or myeloid). Lymphoma Lymphoma is cancer that begins in lymphocytes (T cells or B cells). These are disease-fighting white blood cells that are part of the immune system. In lymphoma, abnormal lymphocytes build up in lymph nodes and lymph vessels, as well as in other organs of the body. There are two main types of lymphoma: Hodgkin lymphoma – People with this disease have abnormal lymphocytes that are called Reed-Sternberg cells. These cells usually form from B cells. Non-Hodgkin lymphoma – This is a large group of cancers that start in lymphocytes. The cancers can grow quickly or slowly and can form from B cells or T cells. Multiple Myeloma Multiple myeloma is cancer that begins in plasma cells, another type of immune Bio-3 – Cell and Molecular Biology 27 LEARNING MODULE SURIGAO STATE COLLEGE OF TECHNOLOGY cell. The abnormal plasma cells, called myeloma cells, build up in the bone marrow and form tumors in bones all through the body. Multiple myeloma is also called plasma cell myeloma and Kahler disease. . Melanoma Melanoma is cancer that begins in cells that become melanocytes, which are specialized cells that make melanin (the pigment that gives skin its color). Most melanomas form on the skin, but melanomas can also form in other pigmented tissues, such as the eye. Brain and Spinal Cord Tumors There are different types of brain and spinal cord tumors. These tumors are named based on the type of cell in which they formed and where the tumor first formed in the central nervous system. For example, an astrocytic tumor begins in star-shaped brain cells called astrocytes, which help keep nerve cells healthy. Brain tumors can be benign (not cancer) or malignant (cancer). Other Types of Tumors Germ Cell Tumors Germ cell tumors are a type of tumor that begins in the cells that give rise to sperm or eggs. These tumors can occur almost anywhere in the body and can be either benign or malignant. Neuroendocrine Tumors Neuroendocrine tumors form from cells that release hormones into the blood in response to a signal from the nervous system. These tumors, which may make higher-than-normal amounts of hormones, can cause many different symptoms. Neuroendocrine tumors may be benign or malignant. Carcinoid Tumors Carcinoid tumors are a type of neuroendocrine tumor. They are slow-growing tumors that are usually found in the gastrointestinal system (most often in the rectum and small intestine). Carcinoid tumors may spread to the liver or other sites in the body, and they may secrete substances such as serotonin or prostaglandins, causing carcinoid syndrome. Is Cancer Genetic? Genetic factors can contribute to the development of cancer. A person’s genetic code tells their cells when to divide and expire. Changes in the genes can lead to faulty instructions, and cancer can result. Genes also influence the cells’ production of proteins, and proteins carry many of the instructions for cellular growth and division. Some genes change proteins that would usually repair damaged cells. This can lead to cancer. If a parent has these genes, they may pass on the altered instructions to their offspring. Some genetic changes occur after birth, and factors such as smoking and sun exposure can increase the risk. Other changes that can result in cancer take place in the chemical signals that Bio-3 – Cell and Molecular Biology 28 LEARNING MODULE SURIGAO STATE COLLEGE OF TECHNOLOGY determine how the body deploys, or “expresses” specific genes. Finally, a person can inherit a predisposition for a type of cancer. A doctor may refer to this as having a hereditary cancer syndrome. Inherited genetic mutations significantly contribute to the development of 5–10 percent of cancer cases. How do gene mutations interact with each other? The gene mutations you're born with and those that you acquire throughout your life work together to cause cancer. For instance, if you've inherited a genetic mutation that predisposes you to cancer, that doesn't mean you're certain to get cancer. Instead, you may need one or more other gene mutations to cause cancer. Your inherited gene mutation could make you more likely than other people to develop cancer when exposed to a certain cancercausing substance. It's not clear just how many mutations must accumulate for cancer to form. It's likely that this varies among cancer types. Types of Cancer Treatments Innovative research has fueled the development of new medications and treatment technologies. Doctors usually prescribe treatments based on the type of cancer, its stage at diagnosis, and the person’s overall health. The side effects of chemotherapy include hair loss. However, advances in treatment are improving the outlook for people with cancer. Below are examples of approaches to cancer treatment: Chemotherapy aims to kill cancerous cells with medications that target rapidly dividing cells. The drugs can also help shrink tumors, but the side effects can be severe. Hormone therapy involves taking medications that change how certain hormones work or interfere with the body’s ability to produce them. When hormones play a significant role, as with prostate and breast cancers, this is a common approach. Immunotherapy uses medications and other treatments to boost the immune system and encourage it to fight cancerous cells. Two examples of these treatments are checkpoint inhibitors and adoptive cell transfer. Precision medicine, or personalized medicine, is a newer, developing approach. It involves using genetic testing to determine the best treatments for a person’s particular presentation of cancer. Researchers have yet to show that it can effectively treat all types of cancer, however. Radiation therapy uses high-dose radiation to kill cancerous cells. Also, a doctor may recommend using radiation to shrink a tumor before surgery or reduce tumor-related symptoms. Stem cell transplant can be especially beneficial for people with bloodrelated cancers, such as leukemia or lymphoma. It involves removing cells, such as red or white blood cells, that chemotherapy or radiation has destroyed. Lab technicians then strengthen the cells and put them back into Bio-3 – Cell and Molecular Biology 29 LEARNING MODULE SURIGAO STATE COLLEGE OF TECHNOLOGY the body. Surgery is often a part of a treatment plan when a person has a cancerous tumor. Also, a surgeon may remove lymph nodes to reduce or prevent the disease’s spread. Targeted therapies perform functions within cancerous cells to prevent them from multiplying. They can also boost the immune system. Two examples of these therapies are small-molecule drugs and monoclonal antibodies. Biomarker Testing for Cancer Treatment Biomarker testing is a way to look for genes, proteins, and other substances (called biomarkers or tumor markers) that can provide information about cancer. Biomarker testing can help you and your doctor choose a cancer treatment. Activity No. 4 Instruction: Create a model that explains the relationship between the cell cycle and the development of cancer. Your model can be an illustration, a description, a video explanation, or a physical representation. Self-Check 10.4 Give substantial answers to the following questions: 1. What does G0 mean in the cell cycle? 2. What is the main difference between apoptosis and necrosis? 3. What happens with apoptotic cells? 4. Briefly describe the intrinsic and extrinsic pathways for apoptosis. 5. Is there a vaccine for cancer? 6. What are the stages of cancer and describe each stage? 7. What are the general signs and symptoms of cancer? 8. What are some preventions tips to reduce your risk of getting cancer? Bio-3 – Cell and Molecular Biology 30 LEARNING MODULE SURIGAO STATE COLLEGE OF TECHNOLOGY LOOKING BACK Review the following concepts: Haploid – Organism with only one copy of each gene in each cell, or gametes with such. Diploid – Two copies of each gene, per cell. PolyploidDominance – Multiple (more than two) copies of each gene per cell. Sister Chromatids – The replicated DNA that exist as a single chromosome until separated in anaphase. Apoptosis is a form of programmed cell death, or “cellular suicide.” It is different from necrosis, in which cells die due to injury. Apoptosis is not the only form of programmed cell death, but it is the form we understand best. Apoptosis is an orderly process in which the cell’s contents break down and are packaged into small packets of membrane for “garbage collection” by immune cells. It contrasts with necrosis (death by injury), in which the dying cell’s contents spill out and cause inflammation. Apoptosis removes cells during development. It also eliminates pre-cancerous and virus-infected cells, although “successful” cancer cells manage to escape apoptosis so they can continue dividing. Apoptosis maintains the balance of cells in the human body and is particularly important in the immune system. Post test Multiple Choice. Encircle the letter of the best answer. 1. A cell is going through meiosis. The sister chromatids are lined up on the metaphase plate. What phase of meiosis is described here? c. Metaphase I c. Metaphase d. Prophase II d. Anaphase I 2. An adult organism has 60 chromosomes or 30 homologous chromosomes. 30 are maternally derived, 30 are paternally derived. How many chromosomes are in each cell after mitosis? a. 60 chromosomes, 30 homologs. b. 120 chromosomes, 60 homologs. c. 30 chromosomes, no homologs. d. 30 chromosomes, 60 homologs Bio-3 – Cell and Molecular Biology 31 LEARNING MODULE SURIGAO STATE COLLEGE OF TECHNOLOGY 3. An adult organism has 60 chromosomes or 30 homologous pairs of chromosomes. 30 are maternally derived, 30 are paternally derived. How many chromosomes are in each cell after meiosis? a. 30 chromosomes, no homologous chromosomes. b. 60 chromosomes, 30 homologous chromosomes. c. 120 chromosomes, 60 homologous chromosomes. d. 30 chromosomes, 60 homologs 4. Which of the following is mitosis not applicable? a. Repair (of a wound) in multicellular organisms b. Asexual reproduction in unicellular organisms c. Development (e.g., baby in mother's womb) d. Production of gametes 5. Which choice best describes the cell cycle? Cells grow and develop during interphase. Cells reproduce during the a. mitotic phase. b. Cells grow and develop during the mitotic phase. Cells reproduce during interphase. c. The nucleus of a cell divides during interphase. The cytoplasm of a cell divides during the mitotic phase. d. The nucleus of a cell divides during the mitotic phase. The cytoplasm of a cell divides interphase. 6. During which stage of interphase do cells perform their normal cell functions (such as growing and making enzymes to digest your food)? a. S stage c. G2 stage b. Mitosis d. G1stage 7. Which of the following is true of crossing over? a. Segments of DNA are traded between unrelated chromosomes. b. Crossing over occurs more often in male gametes than female gametes. c. Most homologue pairs do not have any crossover events d. Most homologue pairs do not have any crossover events 8. Which of the following explains how apoptosis is related to cancer? a. The cues that would trigger apoptosis have failed in cancer cells. b. Cancer cells are formed when necrosis occurs instead of apoptosis. c. Cancer is an example of uncontrolled apoptosis. d. Cancer cells cause excessive apoptosis in surrounding cells to make room for more cancer cell growth. 9. Which of the following scenarios demonstrates apoptosis? a. An immune cell self-destructs once it is no longer needed by the immune system. b. Muscle fibers are signaled to contract and move. c. A severe burn causes skin cells to die. d. All are correct responses Bio-3 – Cell and Molecular Biology 32 LEARNING MODULE SURIGAO STATE COLLEGE OF TECHNOLOGY 10. Which of the following is true of normal adult cells but NOT cancer cells? a. Division in the presence of external growth signals b. Contact with other cells increases likelihood of division c. Large amount of telomerase present d. Cell death after a finite number of cell division References Karp, G. Karp, G.( 2013) Cell and Molecular Biology, Wiley and Sons Pollard, T.D. and Earnshaw, W.C. 2008. Cell Biology. Saunders Elsevier, USA Raven, J. 2018. Biology. McGraw Hill. USA. https://courses.lumenlearning.com/biology1/chapter/the-cellcycle/#:~:text=The%20cell%20cycle%20is%20an,two%20identical%20(clone)%20ce lls. https://www.britannica.com/science/mitosis https://www.britannica.com/science/meiosis-cytology https://biologydictionary.net/meiosis/ https://www.khanacademy.org/science/biology/developmental-biology/apoptosis-indevelopment/a/apoptosis https://www.cancer.gov/about-cancer/understanding/what-is-cancer https://www.medicalnewstoday.com/articles/323648 Bio-3 – Cell and Molecular Biology 33