Lecture 14 - Oncogenes and tumour suppressor genes Flashcards
What do tumour suppressors do?
A tumour suppresses tumours by regulating cell proliferation and are inactive in tumour formation.
What is a major difference between an oncogene and tumour suppressor?
Oncogenes have a dominant phenotype - only need one to cause cancer
Tumour suppressors - 2 recessive phenotpye so need both to cause cancer
Fusion experiments proved this
What are Retinoblastomas caused by?
Retinoblastoma is caused by mutations in the Rb gene, a tumour suppressor gene.
What are the 2 different mitotic recombinations?
Sporadic - not inherited, known as unilateral only happens in one eye. Needs 2 mutations.
Familial - already have a mutated version and get another in order to get it. One-hit mutation. Bilateral, in both eyes. Inherits one copy of Rb gene from a parent
Loss of heterozygosity
What is NF1 and what happens when it mutates ?
NF1 is a Ras GAP (normally inhibits Ras activity)
When your NF1 mutates, neurofibromatosis occurs. This is a tumour in the peripheral nervous system.
This causes an increase in Akt and TOR pathway
What does APC do ?
APC is a tumour suppressant gene that downregulates B catenin and a loss of APC cause colon cancer
Stem cells in the crypt usually migrate out because of B catenin. So B catenin is usually very high at eh base of crypt and APC high at top of crypt
WNT zone is at the bottom cells proliferate and move up then differentiate. Then they die or they move out of crypt
What happens when APC is mutated and lost?
APC mutation blocks migration of cells out the crpyt and B catenin is very high along the entire crypt now.
Causing transcription of GFs, including MYC an oncogene cancer
What is PVHL, what does it modulate and what does it destroy and what is it encoded by ?
PVHL (tumour suppressant) - controls the levels of HIF/ 1-alpha. It modulates the hypoxic response
This causes the destruction of HIF.
PVHL is encoded by VHL gene
hif IS bad
What is Vonhipen Lin-dou syndrome
Caused by loss of function mutation in VHL which causes high HIF1-alpha. This allows cell survival under hypoxic conditions (decreased O2).
This promotes angiogenesis, erythropoiesis and glycolysis.
What is a Fusion experiment?
Get a cancer cell and a normal cell and fuse together
If the cancer gene is dominant you get tumour formation.
If the cancer gene is recessive you do not get a tumour formation
What is RSV?
Ruth Sarcoma virus - multiplies within chicken tissues. Induces cancer. Generates Foci (cancer cell clusters)
Viral transforming gene was initiating and maintaining.
How to stop cancer development
1. Suppression of cell proliferation in response to growth inhibitory and differentiating reducing factors
- Component of cellular machinery inhibits proliferation in response to DNA damage
