Oncogenes are "gain of function" genes. They gain the ability to drive non-stop
growth. In spite of their dominant activities, a single mutated oncogene usually isn't
enough to cause cancer all by itself because tumor-suppressor genes are acting to put
the brakes on to keep cell growth from getting out of control.
Oncogenes aren't usually involved in inherited forms of cancer because most occur as
somatic mutations and can't be passed from parent to child.
A few important oncogenes:
- HER-2/neu
- HER-2/neu encodes for a cell surface receptor that can stimulate cell
division. The HER-2/neu gene is amplified in up to 30% of human breast
cancers.
- RAS
- The Ras gene products are involved in kinase signaling pathways that
ultimately control transcription of genes, regulating cell growth and
differentiation.
- MYC
- The Myc protein is a transcription factor and controls expression of several
genes.
- SRC
- Src was the first oncogene ever discovered. The Src protein is a tyrosine
kinase, which regulates cell activity.
- hTERT
- hTERT codes for an enzyme (telomerase) that maintains chromosome
ends.
Other Bad Guys:
While the prime suspects for cancer-linked mutations are the oncogenes, mutated tumor
suppressor genes, and faulty DNA repair genes, the mutations listed below also do
damage.
Mutations also are seen in genes that:
- Activate and deactivate carcinogens
- Govern the cell cyc
- Control cell senescence (or "aging")
- Control cell suicide (apoptosis)
- Control cell signaling
- Control cell differentiation
- Enable cancer to invade and metastasize to other parts of the body.
Tumor-Suppressor Genes: The good guys, turn cell growth off (stop/brake pedal)
Tumor suppressor genes in normal cells act as braking signals during phase G1 of the
cell cycle, to stop or slow the cell cycle before S phase. If tumor-suppressor genes are
mutated, the normal brake mechanism will be disabled, resulting in uncontrolled growth,
i.e. cancer.
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Tumor suppressorgenes are normal genes whose ABSENCE can lead to cancer.
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Image courtesy of the National Cancer Institute |
Mutations in tumor-suppressor genes cause loss-of-function. Loss-of-function
mutations generally only show up when both copies of the gene are mutated. In other
words, if a pair of tumor suppressor genes are lost or mutated, their functional absence
might allow cancer to develop.
Individuals who inherit an increased risk of developing cancer often are born with one
defective copy of a tumor suppressor gene.
Because genes come in pairs (one inherited from each parent), an inherited defect in one
copy will not lead to cancer because the other normal copy is still functional. But if the
second copy undergoes mutation, the person then may develop cancer because there no
longer is any functional copy of the gene.
A few important tumor-suppressor genes:
- p53: a transcription factor that regulates cell division and cell death.
- Rb: alters the activity of transcription factors and therefore controls cell
division.
- APC: controls the availability of a transcription factor.
More Good Guys - DNA Repair Genes: Correct errors
DNA repair genes code for proteins whose normal function is to correct errors that arise
when cells duplicate their DNA prior to cell division.
DNA repair genes are active throughout the cell cycle, particularly during G2 after DNA
replication and before the chromosomes divide.
Mutations in DNA repair genes can lead to a failure in repair, which in turn allows
subsequent mutations to accumulate. Certain forms of hereditary colon cancer involve
defects in DNA repair.
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Image courtesy of Dr Harold Brenner |
If the rate of DNA damage exceeds the capacity of the cell to repair it, the accumulation
of errors can overwhelm the cell and result in cancer.
A few important DNA repair genes:
CISN Summary: Oncogenes, Tumor-Suppressor Genes and
DNA Repair Genes
This is a lot of information to understand, so we have a short summary for those who just want to remember the basics.
For those that want to know more - reread the section, print the entire section, maybe even take notes to help you memorize the information, if that is important to you. It always helps to have study buddies, take breaks and remember you don't have to memorize all the material. It is here to help you when you need to understand something specific.
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- Most cancer cells acquire a number of common abnormalities
- The causes and sequence of the abnormalities varies
- Effective therapies reverse at least several of the abnormalities
- Mutated genes: see table
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Name of Gene |
This Mutation Causes |
Examples |
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Oncogene |
Uncontrolled growth:
step on the gas |
Her2-neu, Ras, Myc, Src, Htert |
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Tumor Suppressor |
Uncontrolled growth:
remove the brake |
P53, Rb, APC |
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DNA Repair |
No longer able to correct cell
division mistakes |
BRCA1 and BRCA2 |