Cancer

Question 1

Proto-oncogenes

Answer 1

Encode components of growth factor signal transduction, dominant GOF in cancer

Question 2

RNA tumor viruses

Answer 2

Retroviruses w/ RNA genomes that synthesize cDNA using reverse transcriptase –> provirus integrated into the host genome

Question 3

Acute transforming viruses

Answer 3

Viral oncogenes have cellular counterparts that are proto-oncogenes, virus acquires oncogene by accident and makes it permanent part of genome. Of no use to the virus, not involved in proliferation – simply an accident.

Question 4

Non-defective tumor viruses

Answer 4

No oncogene in its genome, but by chance cDNA integrated next to an oncogene like myc. Strong viral promoter now controls oncogene.

Question 5

Retinoblastoma

Answer 5

Tumor suppressor that bonds E2F and sequesters it to inhibit cell division –> inactivated by phosphorylation via Cdk4 kinase, regulated by p16 (also a tumor suppressor gene). Autosomal dominant LOF in Rb gene.

inactive p16 –> active Cdk4 –> inative Rb –> active E2F

active p16 –> inactive Cdk4 –> active Rb –> inactive E2F

Question 6

p53

Answer 6

Tumor suppressor that prevents cell division while DNA is damaged, promotes repair or apoptosis.

Inactivated by Mdm2 protein which promotes degradation through proteasome by preventing phosphorylation.

Question 7

HPV tumor virus

Answer 7

DNA tumor virus that lacks DNA polymerase, tricks host cell into replicating its viral genome by throwing host into S phase using E6 and E7 oncogenes.

Tumor is not part of viral life cycle but rather from a mistake – E6 and E7 get integrated into chromosome at E2 gene, which usually represses E6 and E7.

E6 binds and sequesters p53

E7 binds and sequesters Rb

Question 8

Angiogenesis

Answer 8

Low oxygen –> high HIF with dimerized alpha and beta subunits that enter nucleus –> TF turns on genes needed for angiogenesis including VEGF

High oxygen –> low HIF b/c alpha subunit is hydroxylated by prolylhydroxylase