Seminar 1 - Oncogenes and cell signalling Flashcards
What changes in the cell can cell signalling cause?
Changes in:
- Cell metabolism
- Gene transcription leading to protein expression
- Cell shape
Define a proto-oncogene.
A gene coding for a protein that regulates cell growth and differentiation
What classes of mutations give rise to cancer?
- Deletion - bp(s), gene, chromosome
- Insertion - bp(s), viruses
- Substitution - bp(s)
- Amplification - gene, region, chromosome
- Translocation - chromosome
State the functions of proteins encoded by oncogenes and give an example of each.
- Growth factors: e.g. PDGF (sis)
- Growth factor receptors: EGFR (erbB)
- Protein kinases/proteins that activate protein kinases - Src, Ras, Raf
- Proteins that control the cell cycle - cyclin D (bcl-1)
- Proteins that affect apoptosis - bcl-2
- Transcription factors - myc
What is insertional mutagenesis?
DNA viruses incorporating a viral oncogene inserted into the host DNA
State 2 examples of insertional mutagenesis.
- HPV 16/18 - cervical cancer
2. Hepatitis B virus - hepatocellular cancer
Outline the genetic abnormalities in chronic myeloid leukaemia.
9;14 chromosomal translocation
c-abl (9) truncated onto bcr (22)
Fusion protein has abnormal tyrosine kinase activity
Outline the genetic abnormalities in Burkitt’s lymphoma.
8;14 chromosomal translocation
c-myc (8) onto igh (14)
Strong promoter leading to constitutive MYC expression
Inappropriate expression of myc in B cells leading to a B cell lymphoma
State the mechanisms of oncogene activation.
- Insertional mutagenesis
- Chromosomal translocation
- Chromosomal amplification
Outline the role of RAS.
- Activated by receptor tyrosine kinases
- GTP-binding monomeric switch proteins
- Activate MAP kinase pathway
Summarise the MAP kinase pathway.
- Grb2, SOS, Ras
- Active Ras –> Raf (MAP KKK)
- MEK 1/2 (MAP KK)
- ERK 1/2 (MAP K)
- Sap1a, Elk1, Net
- Transcriptional regulation
