COMPLETE SOLUTIONS VERIFIED
What is an Oncogene and what is it capable of doing?
1. They can evade growth suppressors
2. Drive cell proliferation
3. Resist cell death (Apoptosis)
4. Induce angiogenesis
5. Enable replicative immortality
6. Activate invasion and metastasis
What are Proto-oncogenes
Proto-Oncogene become oncogenes during carcinogeneisProto-Oncogene become
oncogenes during carcinogeneis
What is evidence of oncogene behaviors in Vivo?
-Cause cancer when activated in a transgenic animal
-Render nontumorigenic tumorigenic
-Knock down or knock in tumorigenic cells renders the cells nontumorigenic
-Activation/overexpression of the oncogene is strongly correlated with human cancer
What is evidence of oncogene behaviors in Vitro?
,-Causes anchorage-independent growth in soft agar (Protection from anoikis) Cells can
grow on agar.
-Causes focus formation (loss of contact inhibition)
-----Cells will pile on top of each other
-Renders cells growth independent
What is the role of oncogenes in cancer?
Aberrant expression of proto-oncogenes that increases cell proliferation/survival.
Where were oncogenes first identified?
In cancer causing viruses.
What type of genetic mechanism do oncogenes typically represent?
A dominant mechanism.
Is oncogene activation usually limited to somatic tissue?
Yes, but there are more cases of inherited oncogene mutations.
Which genes can be mutated into oncogenes?
Gproteins such as Ras
Protein kinases such as Raf, Akt, BCR-ABL, Cdk4, sRC
Lipid kinases such as PI3-Kinase
Transcription factors such as Myc, Fos, Jun, etc.
Binding and inactivating apoptic proteins such as BCL2
Protein kinase regulatory subuits such as Cyclins A,E and D
Transcriptional coactivators Beta Catenin, Yap, etc.
, What are the 5 ways to activate oncogenes?
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
Method to activate oncogenes: Mutation of gene to make it overactive
Example: HRAS has Gly12Val point mutation that slows GTP hydrolysis by activating
ras protein. This leaves Ras to be continually activated
What results from multiple gene copies in oncogene activation?
Too much transcript and protein
Homologenously staining regions (HSRs) which are tandem insertions in an existing
chromosome
What is a common approach for amplification detection?
Looking at specific gene/protein
What methods can survey the genome/transcriptome/proteome for amplification
detection?
Methods to test known genes and discover new ones
What are some DNA screening methods?
DNA sequencing, Southern blot, DNA-PCR, and/or FISH
What are some RNA screening methods?
RNA sequencing, RT-PCR, Northern blot, microarray analysis, RNA in situ hybridization