Cell Death and Cancer SNC2D First a bit more cell division… How do prokaryotes divide? Do all eukaryotes divide their cells using mitosis? Do all cells divide at the same speed? What factors affect mitosis? How do cells die? 1. Binary Fission ◦ Type of cell division used by prokaryotes (bacteria) 2. Budding Asexual reproduction in which a new organism develops from an outgrowth or bud on another one 3. Regeneration the process of restoration, and growth after damage 4. Fragmentation A form of asexual reproduction where an organism is split into fragments and each fragment develops into mature, fully grown individuals which are clones of the original organism What other factors impact mitosis? ◦ Altitude, antibiotics… ◦ Can you think of any others? Chemotherapy Radiation Sunlight How do Cells die? Death due to unexpected and accidental cell damage. This is an unregulated cell death. Causes: toxins, radiation, trauma, lack of oxygen due to the blockage of blood flow. A cell also dies as a normal part of the functioning of healthy multicellular organisms. This is a regulated, or controlled, cell death of cells that are no longer useful. Apoptosis also removes cells that have lost their ability to perform efficiently. Apoptosis The material of the cell is recycled by the body. Comparison Necrosis Apoptosis Pathologic “Cell Homocide” Large number of cells Swelling Random, diffuse fragmentation of nucleus Inflammation Surrounding normal tissue damage Physiologic “Cell Suicide” Few cells Shrinkage Orderly nuclear condensation and fragmentation No inflammation No secondary tissue damage Apoptosis Videos http://www.youtube.com/watch?v=7WRk Y8q_F3k http://www.youtube.com/watch?v=gYWU TBM8tTo Cell Lifespans Cells do not live forever. They can only divide a certain number of times until they receive a message or instructions to die. Cell division is necessary for cells to be replaced after they die. In your body, 3 billion cells die every minute. We undergo cell division as part of regeneration, a process essential for repairing damaged tissue. Why do we age? ◦ Not entirely sure ◦ as cells die, they are not replaced or just not as quickly. This results in changes to the structure and function of major body systems. What happens when damage to a cell impairs its ability to commit apoptosis and it divides and divides and divides? Cancer Cancer = uncontrolled cell division Caused by changes in the genes controlling cell division loss of a cell’s ability to undergo apoptosis (“immortal”) ◦ On/off switch is broken ◦ Continually reproducing = Tumour Cancer In small groups ◦ – Compare Normal Cells to Cancer Cells Normal Cells Cancer Cells Make exact copies of themselves through mitosis Make exact copies of themselves through mitosis Reproduce for about 5060 cell divisions Stick together to form masses of cells as appropriate Do not stop reproducing Self-destruct when too old or too damaged May move to another location of the body Do not stick to other cells Behave independently Review: cycle Review: TheThe cellcell cycle hashas fourfour phases phases andcell controls cell division and controls division Two gap or growth phases (G1 and G2) Interphase S phase DNA synthesis M phase Mitosis Cell Cycle Checkpoints There are three checkpoints in the cell cycle ◦ G1-S transition ◦ G2-M transition ◦ Exit M phase transition Checkpoints are where the cell assesses whether conditions are favorable for cell division. When the environment is not favorable (for example, when the cell’s DNA is damaged), a protein called p53 can stop the cell cycle and cause the cell to die. When the proteins that regulate the cell cycle are mutated or absent, cells can divide controllably, leading to cancer. Tumor suppressors and oncogenes Mutations in oncogenes and tumor suppressor genes can lead to cancer http://science.education.nih.gov/suppleme nts/nih1/cancer/activities/activity2_animati ons.htm ◦ (animation #5) Cell Cycle Checkpoints A cell should remain in interphase and not divide if… ◦ Signals from surrounding cells tell the cell not to divide ◦ There are not enough nutrients in the cell ◦ The DNA has not yet been replicated ◦ The DNA is damaged These checkpoints are regulated by special proteins like p53 Microscopic Appearance of Cancer Microscopic Appearance of Cancer Cells Cells Definitions Definitions Tumour: • ◦Tumour: a mass of cells resulting A mass of cells resulting from rapidfrom cell growth rapid cell growth Benign: ◦ Tumours that stay confined in a small area, causing little damage Malignant: ◦ Dangerous tumours that break away and move to other areas of the body. • Metastasize • Spread of cancer Cancer Tends to Involve Multiple Mutations Benign tumor cells grow only locally and cannot spread by invasion or metastasis Malignant cells invade neighboring tissues, enter blood vessels, and metastasize to different sites Time Mutation inactivates suppressor gene Cells proliferate Mutations inactivate DNA repair genes More mutations, Proto-oncogenes mutate to oncogenes more genetic instability, metastatic disease Causes of Cancer Mutation: ◦ Random changes that can occur when DNA is replicated Carcinogen: ◦ Any environmental factor that can cause a mutation Videos on Cancer http://www.youtube.com/watch?v=j_wRp a2b5XI http://www.youtube.com/watch?v=8n0ijZ pYXwo http://www.pbs.org/wgbh/nova/body/howcancer-grows.html ANDI – Inserted DNA Monkey with green glow protein from a jellyfish inserted into its DNA. TgCat1 - Green Glow Cats These GM cats carry: ◦ Green fluorescent protein (GFP) gene ◦ and an extra monkey gene, called TRIMCyp, which protects rhesus macaques from infection by feline immunodeficiency virus or FIV – responsible for cat AIDS Glow in the dark dog with an on/off switch! The switch is a chemical trigger Give the dog an antibiotic along with food, she’ll start to glow under UV light Tegon was cloned and in the process her genes were modified to instruct her cells to react to an antibiotic by glowing This research will help find cures to diseases (like Alzheimer's and Parkinson's) that are common to both dogs and humans Want one? She costs $3 million. Curious Cloning… Random In 2008 an American couple paid more than $150,000 to have their late pet dog cloned