Extra reading lectures 1-3

Question 1

MUC16 oncogenes in lung cancers

Answer 1

1. MUC16 (+) binds to JAK2, stimulating STAT3 phosphorylation
2. Expression of c-Jun for cyclin D1 activated
3. MUC16 influences G2/M transition via cyclin B1 and phosphorylation of Aurora kinase A
4. Reduced expression of MUC16 leads to malignant cell accumulation during G2/M phase with subsequent apoptosis of breast cancer cells via JNK signalling

Question 2

APC tumour suppressor gene in Wnt pathway

Answer 2

1. Wnt binds Frizzled receotor and co-receptor LRP5/6
2. This activates Dishevelled, which inhibits the destruction complex (Apc, Axin , GSK-3, and B-catenin)
3. Stabilized B-catenin accumulates in the cytoplasm and translocates into nucleus
4. TCF/LEF transcription factors activate target genes in cell proliferation and differentiation
5. In absence of Apc, B-catenin cannot be degraded, and so DNA is constantly transcribed and proteins translated, leading to overexpression of proteins