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intro_s9 - The retinoblastoma and p53 pathways are...

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The retinoblastoma and p53 pathways are inactivated in most, if not all, cancer cells ( Figure by MIT OCW. ) How p53 and Rb pathway function may be disrupted in cancer cells Components of the pathway which are found altered in human cancers are shown in red on the diagram above. p53 and Rb themselves may be inactivated by gene mutation (loss of both copies or also as in familial retinoblastoma and Li-Fraumeni syndrome where there are inherited mutations in one copy of Rb or p53 gene respectively. Alternatively, inactivation of the p53 and Rb proteins via the action of HPV oncoproteins E6 and E7 respectively. Gene mutation may lead to the production of "activated Ras" which signals continuously. Gene amplification or overexpression may lead to overproduction of Myc, again promoting the cell cycle. Overexpression of cyclin D1 (eg by gene amplification) is found in some tumours. p16 loss by gene mutation (both copies) - note familial melanoma syndrome where there is an inherited mutation in one copy of p16 gene. Overexpression of MDM2 protein (E3 ligase controlling the levels of p53), eg by gene amplification, will lead to increased instability of p53 protein.
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A mutation in the apoptotic pathway downstream of p53 will block the induction of programmed cell death by p53. ( Figure by MIT OCW. )
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