234b Oncogenes Flashcards
oncogene overview? characteristics? one or both alleles for cancer?
gain of function via mutation or over-expression (via mutation in regulatory DNA)-> increased cancer risk
immortalized (rebuilds telomeres)
grows in serum-free conditions (doesn’t need growth factors)
need damage to only 1 allele (dominant)
BCR-ABL associated tumor? mechanism? gene product? drug that blocks?
CML, ALL (leukemia)
fusion of two proteins that results in overactivation –> abl kinase added on to Bcr (9:22 fusion - Philadelphia chromosome)
tyrosine kinase
imatinib - binds ATP binding site on Bcr-Abl
bcl-2
associated tumor?
gene product?
follicular and undifferentiated lymphomas
anti-apoptotic molecule (inhibits apoptosis)
BRAF
associated tumor?
gene product?
melanoma
serine/threonine kinase
c-kit
associated tumor?
gene product?
GI stromal tumor (GIST)
cytokine receptor (for stem cell factor)
c-myc
associated tumor?
gene product?
burkitt lymphoma
transcription factor – point mutation –> impaired degradation
HER2/neu (c-erbB2) associated tumor? mechanism? gene product? drug?
breast, ovarian, gastric carcinomas
amplified receptor expression
tyrosine kinase receptor
trastuzumab
L-myc
associated tumor?
gene product?
Lung tumor (L)
transcription factor
N-myc
associated tumor?
gene product?
Neuroblastoma (N)
transcription factor
ras associated tumor? normal regulation? normal function? gene product of ras?
colon cancer, lung cancer, pancreatic cancer
regulated by GTP-binding and hydrolysis via GAP (turns off) with GDP and GEF (turns on) with GTP
activates down stream events after receptor tyrosine kinase binds signaling molecule –> turns on MAP kinase pathway, proliferation, protein synthesis AKA activates many pathways)
GTPase –> allows ras to be activated without receptor tyrosine kinase pathway
ret
associated tumor?
gene product?
MEN 2A and 2B
tyrosine kinase
typical signaling transduction pathway and examples
1) growth factor
2) GF receptors (EGFR, Her2)
3) Signal transduction proteins (GTPase - Ras, tyrosine kinase - Abl, Src, serine-threonine kinase-PI3K)
4) transcription factor (Myc)
5) cell cylin control (cyclins)
6) regulators of apoptosis (Bcl2)
what transfers a phosphate group from ATP to an amino acid side chain? what removes it?
protein kinase
protein phosphaTase (Takes away P)
PI3K (PI3 kinase) pathway
lipid kinase that P Akt –>
increase proliferation, promotes cell growth (protein synthesis), and inhibits apoptosis
PI3K (PI3 kinase) pathway
lipid kinase that P Akt –>
increase proliferation, promotes cell growth (protein synthesis), and inhibits apoptosis