Are oncogenes gain or loss-of-function?
Does a GOF function dominantly or recessively?
How does the RAS oncogene function?
- RAS generally binds GTP to activate growth
- After time, RAS is hydrolyzed by GAP (like NF1) to hydrolyze GTP and inactivate
- When RAS is an oncogene, it cannot hydrolyze the GTP so it is always on, even in the absence of a mitogen
How does MYC act as an oncogene?
- MYC is not mutated
- 1) Active promoter: more transcription of MYC RNA
- 2) Increased gene copies: multiple on one chromosome, MYC gene amplified
What is Burkitt's lymphoma?
- ***Ebstein-barr virus, HIV
- translocation b/t chromo. 8 &14
- 14 has an active promoter
- Transcription increased from single gene
How does MYC amplification work?
- DNA problems can cause multiple MYC genes to appear on chromosomes
- Normal mRNA but from multiple genes (leads to more protein)
What is the philadelphia chromosome?
chromosome 9 and ABL coming together with chromosome 22 and BCR
What does the Philadelphia Chrom. produce? How?
- CML (leukemia)
- ABL is generally a tyrosine kinase
- When ABL-BCR the TK is constantly active
What is clonal expansion?
- Mutated cells replicating self
- over time causes higher mutations and more chance of cancer
What are the 3 phases of tumor growth?
- 1) initiation
- 2) promotion
- 3) pogression
What is 1) initiation?
mutation with potential
What is 2) promotion?
proliferation of mutated cells only (not normal cells)
What is 3) Progression?
- oncogene + inactivated tumor suppressor
- benign to malignant
- No tumor promoter required
Initiation or Promotion: Cigarette Smoke and Alcohol??
- Cigarette Smoke: initiator
- Alcohol: promoter
What causes Angiogenesis?
- Cell lacks oxygen and nutrients
- Releases growth factors (VEGF)
When is a tumor malignant?
When it has chewed through the basal lamina and began to protrude into underlying tissue
What chemical is used by the malignant tumor to chew through the basal lamina?
Matrix Metalloproteinases (MMP)
How does a cell travel to a new place? (Seed and Soil)
- Initiate, Promote, and Progress
- MMP to break basal lamina
- enter blood and lymph
- MMP to break into new cell
- **Certain cells are very picky about their soil so they only metastasize to certain places.