oncogenes Flashcards
(22 cards)
What was the first identified oncogene?
Src, found in RSV.
What are proto-oncogenes?
Normal genes that regulate cell growth; can become oncogenes.
What is an oncogene?
A mutated or overexpressed proto-oncogene causing uncontrolled growth.
Name 5 ways proto-oncogenes can become oncogenes.
Point mutation, gene amplification, chromosomal translocation, DNA rearrangement, insertional mutagenesis.
What is insertional mutagenesis?
Viral DNA insertion causing overexpression of a gene.
Which growth factor is overexpressed in osteosarcoma?
PDGF (A-chain dimers)
Which growth factor is overexpressed in breast cancer?
EGF
What is ErbB and how does it become oncogenic?
EGF receptor; truncated form (qualitative) or amplified (quantitative).
What is HER2/Neu and what mutation activates it?
A receptor; Val → Gln point mutation.
What causes CML at the molecular level?
Bcr-Abl fusion protein from a translocation (Philadelphia chromosome).
What does B-Raf mutation cause?
Melanoma, papillary thyroid cancer.
What happens when Ras is mutated at codon 12?
GTP can’t be hydrolyzed → constitutive activation.
What cancers show high Ras mutation rates?
Pancreatic, colon, melanoma, thyroid.
What cancer is associated with Myc amplification?
Neuroblastoma, small cell lung cancer (SCLC).
What does AP-1 consist of?
Fos and Jun transcription factors.
Name three ways to turn off a signal.
Phosphatases, GAPs, protein degradation.
What is the role of GAPs like NF1?
Promote GTP hydrolysis in Ras (turn it off).
What does Cbl do?
Tags RTKs like EGFR for degradation.
What happens if Cbl is lost?
RTKs stay active → oncogenic signaling.
What activates Ras?
GRB2-Sos complex via RTK activation.
What is the MAPK cascade sequence?
Ras → Raf (MAPKKK) → MEK (MAPKK) → MAPK → Fos/Jun → Proliferation.
What turns off MAPK?
MKP-1 phosphatase.