Neoplasia Flashcards
What is the most commonly over expressed GF receptor; 80-100% of epithelial head and neck tumors?
EGF receptor (ERBB1)
What is the over expressed GF receptor associated with ~30% of breast cancers?
HER2/NEU
What is the most commonly mutated photo-oncogene?
RAS
What activates CDKs and represses their inhibitors (CDKIs)?
MYC
In Chronic Myeloid Leukemia t(9:22) creates … with unregulated … –> … pathway activation.
BCR-ABL fusion protein, with unregulated kinase activity –> RAS/RAF pathway activation
What other genes that control RB phosphorylation can mimic RB loss? (3)
- Cyclin D or CDK4 over expression
- Inactivation of CDKIs
- Oncogenic DNA viruses deactivate RB
In the Central Theme of Malignancy, loss of cell cycle control is seen through one of what 4 key regulators?
CDKIs, cyclin D, CDK4, RB
What is the central monitor of stress, the “guardian of the genome”?
TP53
In what 3 ways does the TP53 gene protect the cell?
- Quiescence: activation of cell cycle arrest
- Senescence: induction of permanent cell cycle arrest
- Triggers Apoptosis
The p53 protein normally has a short half-life, bound to what?
MDM2
With stress the p53 protein activates genes that …
Arrest the cell cycle and induces DNA repair genes
How does p53 arrest the cell cycle?
p53 causes transcription of CDKI which inhibits cyclin/CDK complexes and prevents phosphorylation of RB
Like Rb, p53 can be rendered non-functional by what?
DNA viruses (HPV, HBV)
What does TGF-B normally inhibit?
proliferation (cell growth)
TGF-B binds to receptors I and II -> dimerization -> signal transduction to the nucleus via … -> transcriptional activation of … and repression of …
SMAD molecules -> CDKIs and cyclins
