Cancer—
The disease that results when
The Cell cycle is unregulated at cell cycle checkpoints.
Cell cycle checkpoints-Times during the cell cycle when cell cycle
regulatory genes check for DNA defects or
DNA sorting problems or other major cell
defects).
two kinds of cell cycle checkpoint regulator
Proteins
oncogenes—make cell divide too often
tumor suppressors—prevents cell suicide
of cells with defects; cell suicide is called
apoptosis.
Why does it matter when a cell
divides?
• Multicellular organisms are made of many
kinds of cells which each carry out specialized
jobs in the body.
• If there are too many of some and too few of
others, then there is an imbalance in the
body—failure of homeostasis.
• The extra cells use up resources and space,
and they don’t do the jobs of the cells they
replace.
For example, a human body has 220+ kinds of cells that must
cooperate for homeostasis.
Tissues
Organs
Organ
systems
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Cancer
What is it?
What causes it?
Why does it make you sick?
How can you cure it?
1/2011
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http://media.hhmi.org/hl/03Lect1.html start at minute 8 lecture 1
cancer
The disease resulting
when some cells of the
body divide too often
or
fail to die when DNA is
seriously defective,
broken, or incomplete
Because there are too few
of some types of cells
and
too many of others,
homeostasis is lost.
219 /220 human cell types contain identical genomes.
How is this possible?
Simplified summary:
Signal transduction mediated Gene expression.
Starts before conception. Ends after death.
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So, developing normally and continuing to have
normal health depends on the body having
the right numbers of every kind of cell,
correct cell locations,
and having every cell doing it’s correct job
in cooperation
with all the other 219 kinds of cells of the body.
If any one of the human cell types is too abundant or too
scare relative to the others, functions of the body become
imbalanced with each other.
Anxiety
Breast enlargement in men (possible)
For example: too many
Difficulty concentrating
thyroid hormone producing cells Double vision
http://stemcells.nih.gov/info/scireport/chapter1.asp
Eyeballs that stick out (exophthalmos)
Eye irritation and tearing
Fatigue
Frequent bowel movements
Goiter (possible)
Heat intolerance
Increased appetite
Increased sweating
Insomnia
Menstrual irregularities in women
Muscle weakness
Nervousness
Rapid or irregular heartbeat (palpitations
or arrhythmia)
Restlessness and difficulty sleeping 9
Shortness of breath with exertion
e.g., pheochromocytoma—cancer of
the gland that produces adrenaline:
symptoms of “fight or flight” response
sweating
rapid heart beat
high blood pressure
e.g., too many growth hormone producing cells in
pituitary gland—acromegaly if tumor is benign
hand, foot, face, or tongue growth
carpal tunnel syndrome
joint and bone aches
gigantism
Too few of a particular kind of cell
causes problems.
Fetal alcohol syndrome
Progeria—premature
aging—too few cell
divisions
Normally cells divide only when
signaled by molecules from other cells.
These signals are called growth factors.
.
http://www.mbusd.org/staff/pware/video/Cancer.mov
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Why do you get Cancer?
Cell cycle protein coding genes or tumor suppressor genes
become mutated so that cells divide out of sync with the
needs of the entire body. The cells divide even after failing a
checkpoint.
Any one mutated to be active independent of the others can
cause cancer. The rectangles show time of action of just a few
of the oncogenes and tumor suppressor checkpoint proteins.
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Melanoma skin cancer is an example of how cancer occurs if normal
regulation of the cell cycle is disrupted.
Melanoma is one type of skin
cancer, developing when the
pigmented cells in skin have
mutations in cell cycle or tumor
suppressor genes.
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Proteins mutated to stimulate inappropriate cell
division are called oncogenes.
The study of cancer is called oncology.
Oncogenes are mutated forms of proteins needed for normal cell division
Carcinogens: Agents that cause mutations in oncogenes.
Side effects of chemotherapy (use of drugs to kill cancer cells)
occur because drugs that target oncogenes also interrupt
actions of the normal versions of the proteins, killing or preventing normal cells.
.
Side effects of cancer drug treatments
that target both oncogenes & proto-oncogenes
in rapidly dividing normal cells
•
•
•
•
Anemia
Hair loss
Diarrhea & nausea
Weakened immune responses
Steps in cancer development
1) loss of normal cell cycle inhibition due to
mutation in a gene coding an oncogene OR
a tumor suppressor gene.
Slowly growing clumps
called BENIGN—harmless--polyps or tags.
Moles
additional mutations
OF OTHER ONCOGENES OR TUMOR SUPPRESSOR
GENES
may cause cancer
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Cell cycle checkpoint—time in the cell cycle
when normal versions of oncogenes and tumor
suppressors act to prevent abnormal cells from
dividing.
Apoptosis—programmed cell death by suicide
of cells whose cell cycle checkpoint proteins
have detected failure.
Stage 2
A mutation in at least 2
different cell cycle
CONTROL genes
tumors divide faster, may
form large clumps, but
they don’t spread.
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Stage 3.
Even more mutations in cell cycle regulatory genes
occur—cells become malignant. But,
they haven’t yet traveled farther than the lymph
nodes nearest the tumor. Metastasis ---spreading of
tumor cells.
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How cancer cells travel: In
circulating body fluids.
• http://www.pbs.org/wgbh/
nova/cancer/media/2805_0
6q.html
Stage 4. The cells divide rapidly without DNA
proofreading, so mutations accumulate rapidly.
The cells become nonfunctional and more and
more defective, and they spread far from the
original tumor, killing cells of the new location.
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Heredity tendencies for families to
have a higher than typical rate of a
cancer type is due to mutations in
one copy of a tumor suppressor
gene.
• Both copies of the gene are mutated in
people who eventually develop cancer. Not
all members will experience the second
mutation.
• But these people are twice as likely to have
BOTH MUTATED as people not inheriting one
defective tumor suppressor gene.
Cancers are named for their sites of
origin.
• Carcinoma—arises in
coverings or linings
• Leukemia—arises in white
blood cell precursors
• Sarcoma—begins in
connective tissue (like
tendons, ligaments, fat)
• Etc.
• Adenoma—arises in glands
• Glioma-arises in support
cells of the brain
• Neuroma-arises in neurons
Treatments:
• Remove tumors (sometimes chemotherapy is
used before this to kill loose cells)
• Chemotherapy—use drugs to kill rapidly dividing
cells OR to kill cells with a particular defective
oncogene or tumor suppressor gene
• Radiation therapy—induce death of tumor cells
by inducing major DNA breakage
• Immune therapy—inject extracts of the person’s
tumor cells to induce immune response against
the mutated, foreign proteins
The best defense against cancer: Early detection
and treatment
• Regular check-ups
• Self checks for areas like breast and testicles (very
common cancer sites) and moles or other areas if family
history merits
• Awareness of changes in your body like blood in feces or
new pain, blurred vision, etc
• Knowing family medical history of cancers to know what
sites need most thorough checking or chemical tests (for
early cancer protein markers)
• Avoiding exposure to carcinogens like cigarette or
marijuana smoke or intense sunlight or radioactive
materials
2. What is the general name of any gene that codes a protein
normally involved in controlling progression through the cell
cycle?
1.
2.
3.
4.
Proliferation gene
Growth factor gene
Proto-oncogene
Tumor suppressor
gene
5. Oncogene
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3. Mutations in tumor suppressor genes cause
cancer if they are “loss of function” (recessive)
mutations because these proteins are needed to
initiate death of defective cells.
1. True
2. False
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4. Mutations in proto-oncogenes cause
cancer if they are “loss of function”
(recessive) mutations since these increase
likelihood cells will divide.
1. True
2. False
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5.
One role of a tumor suppressor gene is to
induce apoptosis (cell suicide) when cells have
major errors in DNA, preventing their entry into
prophase.
1. true
2. false
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6. Another name for apoptosis is cell
suicide. It is initiated in the
mitochondria.
1. true
2. false
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7. Malignant tumors are more dangerous than
benign tumors because:
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1. Their cells are immortal
2. Their cells are not contact
inhibited
3. Their cells are not density
dependent
4. Their cells have mutated
proto-oncogenes
5. Their cells can enter the
lymphatic system or blood
stream
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