W07_03 Molecular pathogenesis of cancer 2 Flashcards
name 4 important tumour suppressor genes
Rb;
pXX (cyclin dependent kinase inhibitor);
APC;
p53
how does Rb typically work?
binds to E2F transcription factor to prevent transcription. hyperphosphorylated? unbinds and allows transcription
what’s knudson’s two-hit hypothesis?
need two mutations of both alleles of Rb to produce retinoblastoma (some mix of inherited and acquired damages)
what’s “loss of heterozygosity” in the context of cancer?
when the two alleles, which were heterozygous for mutations, both become homozygous for mutations
why do we see upregulation of pXX enzymes in response to genetic disruptions?
they’re cell cycle moderators and try to control the rampant growth
what’s the role of APC (adematous polyposis coli)?
inhibitor of signal transduction; can be disinhibited by WNT signalling
what happens when APC breaks down?
regardless of WNT signalling, APC will not control beta-catenin transcription factor signalling
clinically, what does APC mutation cause?
familial adenomatous polyposis, and colon cancer
where does p53 act in the mitotic cycle?
between G1/S
what does p53 do to cells?
induces: quiescence, senescence, apoptosis
p53 has a short half life by itself. how does the body compensate?
it’s complexed to MDM. released when the cell is stressed
when the cell is stressed, there is induction of p21. what does this do?
cell cycle arrest. gives the cell more time to fix the broken dna.
note: 50% of human tumours show p53 mutations!
dangggg
what is li-fraumeni syndrome?
germline mutation in p53. the person will develop multiple cancer types
what are the key genes in HPV?
E2, E6, E7.
what does the HPV E2 gene do?
suppresses E6 and E7. promotes viral protein-making
what does the HPV E6 gene do?
destroys p53 and bax. cell can’t regulate nor apoptose
what does the HPV E7 gene do?
binds to Rb and displaces E2F, so E2F goes unchecked
what are MLH1, MSH2, MSH6, PMS2?
mismatch repair genes that check for correct base-pairings
what happens when mismatch repair genes are defective?
mutations and microsatellite instability
what is lynch syndrome (HNPCC) caused by on the genetic level?
inherited mismatch repair gene mutation
what genetic defect causes xeroderma pigmentosum?
nucleotide excision repair broken
what gene fixes inter and intra-strand DNA cross-links?
BRCA1 or BRCA2. if these mutated, can lead to higher cancer rates
what’s the non-homologous end-joining pathway?
broken DNA strands (no telomeres at the ends) are joined end-to-end
