MRCPath Self Help Course 12 th January 2010. Mai M Abd El-Aziz.
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MRCPath Self Help Course
12th January 2010
Mai M Abd El-Aziz
Describe the mechanism by which mutations in tumour suppressor genes can lead to the development of cancer?? Concentrate primarily on the RB and p53 genes?? but give examples of other genes if you come across significant differences in the way in which they act??
Complications of the RP paradigm
During the G1 phase
pRb is hypo(P) (Active)binds E2F repression of E2F-mediated transcription
In late G1 and through the M phase
pRb is (P) i.e. inactivated by CDK E2F is released promote the expression of genes required for cell division.
Loss of P16 function loss of pRb function inappropriate cell cycling
The RB pathway cont.
Can be activated by both external and internal aberrations
Activation of p53
B) Deregulation of cellular oncogenes
Expression of P14 (ARF)
Blocking the degradation of P53
Deactivation of MDM2
Activation of P53
APC downregulate the WNT pathway by acting as a shuttle for -catenin