Cell growth + division lecture 10

Question 1

Fos oncogene

Answer 1

• Rapidly induced
• Activation of v-fos involves deletion of ‘instability’ sequences in 3’ non coding
• Fos heterodimerises w/ Jun
• Viral Jun is truncated in regulatory region → stabilised

Question 2

Cyclin D1 expression

Answer 2

• Signalling through integrin → activation of Ras → MAPK active → Fos → Jun → Jun + Fos dimerise → ↑ expression of cyclin D1
• Also TFs like STAT, NF-Kb

Question 3

Myc

Answer 3

• Assoc w/ proliferation
• levels ↑ by GF
• Regulated by PTMs from other pathways e.g. phosphorylation by MAPK or GSK
• Switch btw proliferation + differentiation
• If myc lost, Max heterodimer w/ Mxt → repress mitogenic signals
• Directly activates transcription of Cdc25
• Inactivates p27 + p21
• ↑ cyclin D1 expression
• -

Question 4

Mutations in Cdks

Answer 4

• Cyclin D = over expressed due to amplification

- mutations in cdk4 prevent INK4 binding

Question 5

Passenger and driver mutations

Answer 5

• Driver mutations → cancer
• Passenger mutations can be tolerated, often in introns
• Lung carcinoma has >50,000 singel nucleotide changes

Question 6

Oncogene cooperation

Answer 6

• Oncogenes + tumour suppressors work together
• ↑ genetic instability means pick up ↑ mutation
• E.g. overexpression of Myc and v-ras

Question 7

Cancer stem cell

Answer 7

• Controversial
• Certain cells in a tumour act like cancer stem cell
• Take cells in tumour, disc into single cells + re-introduce
• Small no. that can form tumour = stem cell like

Question 8

Drug treatment

Answer 8

• Previous = DNA damaging agents, ionising radiation
• Inhibit activated oncogenes
• Universal target like Ras, inhibit PTM
• Selective target e.g. Tamoxifen

1. Kinase inhibitor
   - ATP analogues x selective enough
   - tyrosine kinase inhibitor = non-selective or specific inhibitors
2. Herceptin
   - Monoclonal ab against Neu
3. Gleevec
   - Inhibits Bcr-Abl
   - Resistance due to point mutation
4. Targeting oncogene expression
   - ↓ side effects
   - Ribozyme can target BCR-Abl fusion function
   - Delivery of ribozyme hard

Synergistic treatment