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 vi...
GMS 6552 Exam 2 Questions and Answers 100% 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
Inhibitors of HGF/c-Met - ANSWER-activating invasion and metastasis
Inhibitors of VEGF signaling - ANSWER-Inducing angiogenesis
PARP inhibitors - ANSWER-Genome instability and mutation
Proapoptotic BH3 mimetics - ANSWER-resisting cell death
Aerobic glycolysis inhibitors - ANSWER-deregulating cellular energetics
Cellular function of c-Myc - ANSWER-Expression of pro-proliferative genes
Expression of pro-apoptotic genes
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