LEC54: Cancer Pathways and Tumor Biology Flashcards
what are the components of the Rb pathway
how are Rb pathway targets altered in cancer?
in a mutually exclusive manner: it’s not merely Rb that’s the target, the whole pathway is the target
i.e. deletion of p16 is mutually exclusive w/ D1 and Rb, and the same tumor won’t sustain mutations in multiple components of the same pathway unless the pathway’s inactivated
what mutations happen to p16? result?
deletion, missense mutation, promoter methylation
it is deleted in sporadic melanoma, muated in many melanomas
what mutations happen to cyclin D1 gene?
amplification, chromosomal translocation
what muations occur to genes encoding Cdk4 or Cdk6? result?
amplification, missense mutation
prevents binding of p16
occurs in glioblastoma and other brain cancers
mutations that occur to Rb?
deletion, mutation
what does human papilloma virus (HPV) lead to?
expression of E7 protein
this inhibits pRb
what is pRb? when is it deleted -> result?
tumor suppressor
deleted in retinoblastoma, osteosarcoma
what happens re: cyclins in breast cancer?
cyclin D1 is amplified in some breast cancers
overexpression of D1 inactivates Rb
what does p53 pathway normally cause?
arrest or apoptosis
components of the p53 pathway?
what are mechanisms to arrest the p53 pathway?
1) ARF gene deletion, missense mutation, or promoter methylation
2) Mdm2 gene amplification and Mdm2 protein overexpression
3) p53 missense mutation
4) HPV E6 protein targets p53 for degredation
* ONE OF THESE THINGS, NOT ALL, OCCUR, SHOWING MUTUAL EXCLUSIVITY AND THAT THE PATHWAY IS THE TARGET IN CANCER*
what does cervical cancer inactivate in p53 pathway?
p53
cells w/ a mutant Mdm2 have what kind of p53?
what does this demonstrate?
WT p53
demonstrates the PATHWAY is the target, not the actual GENE or PROTEIN
what is the APC pathway?
what is APC, what is its normal function re: beta-catenin?
APC: adenomatous polyposis coli protein
normally, is a scaffold that interacts w/ Beta-catenin, facilitates its degredation, by bringing GSK-3-beta and beta-catenin teogether
what does loss of APC cause?
upregulation of Myc and Cyciln D, via transcriptional effects of beta-catenin
what do mutations in APC cause?
expression of a truncated protein that can’t bind beta-catenin
what do mutations in beta-catenin cause?
changes in its phosphorylation sites, so it cannot be degraded
if it’s not phosphorylated°raded, doesn’t matter if APC or Axin is present
can cause regulatory issues w/ Myc, Cyclin D
mutations in which parts of the Apc pathway are mutually exclusive in many cancers?
mutations in Apc, Axin, B-catenin
what activates the Erk pathway?
growth factors binding to receptor on cell surface
cause pathway to go
what are the components of the Ras/PI3K pathways?