cell cycle/death review deck Flashcards
describe tumorigenesis in colon ca
loss of APC DNA hypomethylation activated KRas loss of 18qTSG loss of p53
why does a hereditary predisposition result in CA at earlier age?
start at initiation phase
what are the 3 ways that proto-oncogenes can be activated?
mutation, chromosomal translocation and amplification
why would chromosomal translocation lead to activation of a proto-oncogene? (2)
- chimeric protein with alt function
- different promoter results in over-expression
when do all oncogenes act on cell?
before or during G1
why do oncogenes act before/during G1?
bc they enable cells to bypass restriction point, or pass it quicklime allowing for uncontrolled cell division
what is the effect of growth factors?
will trigger entry into G1
discuss growth factors in T- cell leukemias
T cell leukemias can use autocrine signaling to promote proliferation by producing their own interleukin-2 and interleukin-2 receptor
describe Her2-Nu
in breast CA, with TKR, val to bglu mutation, receptor dimerizes to try to increase stability and as a result, is activated without ligand
describe EGF-ErbB
in NSC lung CA- deletion leads to a constitutively active TKR
describe a common Ras mutation
reduction of GTPase activity so that TP can bind, but is never hydrolyzed so Ras remains “on”
what d/o has B-Raf mutation? what is this treated with?
melanoma; vemurafenib- mutant kinase inhibitor
what generates bcr-abl? disease? treatment?
c-abl kinase becomes fused with bcr gene; CML; gleevec
what is myc?
transcription factor that activates cyclin D and E2F
which tumors show over expression of myc?
neuroblastomas and B cell lymphomas
what tumors show increased cyclin D?
head/neck, breast
which d/o is characterized by over expression of bcl-2?
bcl-2 (anti-apoptotoic), overexpression in CLL
what defect in TGF-b could lead to tumorigenesis?
mutation in receptor or smads
what are p15 and PAI-1 activated by?
Phosphorylated smads
what is p15?
inhibitor of cyclin D-CDK4 complexes
what is PAI-1?
involved in regulation of ECM proteins
what is the function of Rb protein?
Rb suppressed E2F
describe retinoblastoma cells in regard to Rb protein?
have lost both alleles for Rb protein, in the absence of Rb, E2F does not need cyclin D-CDK4/6 complexes to activate
what is the p21 CIP family?
binds cyclin-CDK complexes and blocks kinase activity (universal inhibitor)
