Mutations Associated with Cancer Flashcards
How do cancer-causing mutations arise?
Randomly, unless the mutation was hereditary
Do cells become cancerous after 1 mutation?
Not usually, but if that cell keeps dividing then the effect can snowball
What are the 3 stages of cancer progression?
Initiation, promotion, tumour progression
What is the initiation stage of cancer progression?
The cells are converted to a precancerous state from a mutation
Where does the initial mutation have to occur to convert a cell to a precancerous state?
In a cell division regulatory gene
What is the promotion stage of cancer progression?
The cell starts to accumulate a few more mutations from gradual, consistent exposure to carcinogens, which stimulates altered cells to divide and form tumours
What is the tumour progression stage of cancer progression?
Snowballing effects. The cells keep dividing, keep acquiring mutations, become malignant, aggressive and invasive
What are the 6 hallmarks of cancer cells?
- Don’t require growth factors to divide
- Don’t respond to signals telling them to stop growing
- Don’t respond to signals telling them to undergo apoptosis
- Immortal and can keep dividing forever
- Sustained angiogenesis
- Metastasis
How is cell division normally regulated?
Through anchorage and density dependent growth
Do normal cells do anchorage and density dependent growth?
Yes. They only divide when anchored to a surface and stop dividing when they run out of space
Do cancer cells do anchorage and density dependent growth?
No. They can divide in suspension and keep piling up even when they run out of space
What are mitogens?
Chemicals like growth factors that activate cell division signalling pathways
What are the steps in the Ras/MAPK pathway?
- Ligand (growth factor) binds to its receptor
- Tyrosine kinase receptor dimerizes and cross-phosphorylates
- Phosphorylated receptor recruits GRB2, which binds through its SH2 domain
- GRB2 recuits SOS (a GEF)
- SOS exchanges the GDP on Ras for GTP and activates it
- Active Ras activates MAPKKK and starts the kinase cascade
- MAPKKK phosphorylates MAPKK
- MAPKK phosphorylates MAPK
- MAPK translocates into the nucleus and activates transcription factors
What do SH2 domains do?
Bind to phosphorylated tyrosines
Which protein in the Ras/MAPK pathway is commonly mutated in cancer?
Ras
