Correct!!
Oncogene- ANSWER-A gene that causes or contributes to the development of cancer
Hallmarks of Cancer- ANSWER-Sustaining proliferative signaling
Evading growth suppressors
Activating invasion and metastasis
Enabling replicative immortality
Inducing angiogenesis
Resisting cell death
In vivo oncogenic evidence
- ANSWER-Cause cancer when activated in a transgenic animal
Render nontumorigenic cells tumorigenic
Knock down or knock out in tumorigenic cells renders the cells nontumorigenic
Activation/overexpression of the oncogene is strongly correlated with human cancer
In vitro oncogenic evidence
- ANSWER-Causes anchorage -independent growth in soft agar
(protection from anoikis)
Causes focus formation (loss of contact inhibition)
Renders cell growth factor independent
Oncogenes in Cancer- ANSWER-Aberrant expression of proto -oncogenes that increases cell
proliferation/survival
First identified in cancer
-causing viruses
Typically a dominant mechanism
Oncogene activation is usually limited to somatic tissue, but more cases of inherited oncogene
mutations are being found
Biochemical functions of oncogenes- ANSWER-G-proteins (Ras)
Protein Kinases (Raf, Akt)
Lipid Kinases (PI3-Kinase)
Transcription Factors (Myc)
Binding and inactivating apoptotic proteins (BCL2)
Protein Kinase regulatory subunits (Cyclins A, E, D)
Transcriptional coactivators (B
-Catenin, YAP, TAZ)
, Five Ways to Activate Oncogenes- ANSWER-1. Mutation of gene to make it overactive
2. Amplification of a normal gene
3. Chromosomal Rearrangement
4. Promoter/enhancer insertion
5. Hypomethylation of oncogene
Amplification- ANSWER-Multiple gene copies = too much transcript and protein
DNA sequencing, DNA-PCR
RNA sequencing, RNA-PCR
Protein: Western
Chromosomal Rearrangement
- ANSWER-Affects regulatory region of oncogene
Cytogenetics
PCR using primers
Promoter/Enhancer Insertion- ANSWER-From retroviral integration near oncogene
Gene expression activated from the viral promoter
Should activate oncogenes or disrupt tumor suppressors
Can find new genes
Hypomethylation of Oncogenes- ANSWER-Ex. N-ras is activated in liver cancer due to under
-
methylated promoter, allowing gene expression
Directly measure methylation using methyl
-sensitive restriction enzyme/genomic DNA,, bisulfite
genomic sequencing, or methylation specific PCR
measure RNA/protein level
Oncogenes in medical practice
- ANSWER-Specific diagnosis, sub
-classification of tumor type, and/or
prognosis can be based on certain gene involvement
EGFR Inhibitors - ANSWER -Sustaining proliferative signaling
Cyclin-dependent kinase inhibitors
- ANSWER-evading growth suppressors
Immune activating anti
-CTLA4 mAb - ANSWER-avoiding immune destruction
Telomerase inhibitors- ANSWER-enabling replicative immortality
Selective anti
-inflammatory drugs- ANSWER-Tumor-promoting inflammation