Oncogenes are cancer promoting genes that are derived from normal genes (proto-oncogenes). Proto-oncogenes play an important physiological role in cellular growth and differentiation. A 'gain of function' results in an increased risk of cancer. Only one mutated copy of the gene is needed for cancer to occur - a dominant effect. They are implicated in the development of up to 20% of human cancers.
Proto-oncogenes may become oncogenes via the following processes:
| Gene | Category | Associated cancers |
|---|---|---|
| ABL | Cytoplasmic tyrosine kinase | Chronic myeloid leukaemia |
| c-MYC | Transcription factor | Burkitt's lymphoma |
| n-MYC | Transcription factor | Neuroblastoma |
| BCL-2 | Apoptosis regulator protein | Follicular lymphoma |
| RET | Tyrosine kinase receptor | Multiple endocrine neoplasia (types II and III) |
| RAS | G-protein | Many cancers especially pancreatic |
| erb-B2 (HER2/neu) | Tyrosine kinase receptor | Breast and ovarian cancer |
Tumour suppressor genes restrict or repress cellular proliferation in normal cells. Their inactivation through mutation or germ line incorporation is implicated in renal, colonic, breast, bladder and many other cancers. One of the best known tumour suppressor genes is p53. p53 gene offers protection by causing apoptosis of damaged cells. Other well known genes include BRCA 1 and 2.
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Tumor suppressor genes → loss of function results in an increased risk of cancer
Oncogenes → gain of function results in an increased risk of cancer
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DCC - on chromosome 18 → responsible for colorectal, pancreatic or oesophageal cancers
Active (hypophosphorylated) Rb = prevents damaged cells from proceeding past the G1 to S checkpoint
Inactive (hyperphosphorylated) Rb allows it to enter mitosis
Proliferation signals --> activate cyclin D, cyclin E and the corresponding cyclin kinases / CDK4 --> hyperphosphorylate Rb protein --> allow the transition from G1 to S phase