Lecture 5 - Cellular Oncogenes Flashcards
Give three common examples of proto-oncogenes being converted in oncogenes (list three molecules).
1 - H-ras
2 - myc
3 - bcr-abl
Is it common for tumors to contain viruses? Give three examples.
NO, it is rare as few tumors contain viruses.
1 - Lymphoma
2 - Cervical cancer/oral cancer (HPV)
3 - Hepititis (liver)
What are endogenous retroviruses?
Endogenous retroviruses insert their genomes into that of the host and stay stilent for a period of time (transcriptionally silent) before being awakened and wreaking havoc.
- Pass on genomically
- Can spontaneously awaken (ex: leukemia)
- Some carcinogens can cause cancer by activating them
How do researchers search for oncogenes in transformed cells? What is transfection and why is it great for cancer research? What does it prove? Give a step-by-step process of transfection.
Transfection: uptake of cancer DNA by healthy cells. Great because it works across species and tissues: human cancer DNA in a lab rat. Proves that viral presence is not required for tumor/cancer formation.
Process:
1 - Add small amount of cancer DNA to healthy cells
2 - if transformation occurs (no virus presence needed)
3 - Cell cluster forms (loss contact inhibition, proliferation)
4 - Inject morphologically changed/altered cells into healthy mouse host
5 - Tumor forms on host
What are some examples of oncogenes that are overexpressed in certain cancers? Give 2.
What is FISH? What does it do? How is it useful?
1 - HER2
2 - Cyclin D1
Fluorescence in situ hybridization (FISH) is a process similar to a southern blot within a cell. Demonstrates level of expression of certain oncogenes within a cell.
Can oncogenes be accidentally overexpressed? How?
Yes, certain oncogenes can be accidentally overexpressed due to location (proximity to other genes) on the genome. Natural Cancer
How is the expression of proto-oncogenes controlled in normal cells vs. retroviruses?
In normal cells, the expression of proto-oncogenes is tightly regulated. In retroviruses, the expression of proto-oncogenes is under the control of the retroviral promoter
What is the ras family of oncogenes? How are they important?
The ras family of oncogenes is one of the most commonly activated oncogenes in human tumors. However, mutations leading to the activation of ras are usually limited to a few critical areas.
In essence, you really need to hit a very specific target with a mutation to activate ras.
How does the myc oncogene become activated? How is it important? Give 3 mechanisms through which this can occur.
The myc oncogene targets ~15% of genes in our genome. If overexpressed, myc can lead to the production of wayyyy too many proteins, leading to proliferation.
Myc activation can occur by:
1 - Viral promoter inserted before myc through provirus integration
2 - Multiple replications of the myc section of the genome by gene amplification
3 - Chromosomal translocation can join two genes, thereby altering them and activating myc
An example of the latter is Burkitt’s Lymphoma.
Give more detail concerning the activation of myc through chromosomal translocation.
How does a location switch for a gene also prevent it’s expression to be regulated?
During chromosomal translocation, the region coding for the myc gene can be transferred to a different region on the chromosome. This can cause myc overexpression by association based on the new location of the gene.
Furthermore, chromosomal translocations can inhibit proper gene regulation by miRNA.
Which two medical conditions contribute heavily to chromosomal translocation?
Chronic malarial infection and malnutrition
