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Western University
Biochemistry 2280A
Derek Mc Lachlin

Brandl Lecture 12 Notes 12/04/2012 Properties of Cancer Cells  Divide in the absence of growth factors o Unregulated growth  Are immortal – do not respond to signals that normally trigger cell death o Normal cells undergo programmed cell death (will divide around 20 times and die), but cancer cells keep dividing and dividing  Are genetically unstable o More point mutations o Copy number variation o Major chromosome abnormalities  Cancer cells can multiply in abnormal places o Normal cells will not grow out of the normal environment, where as cancer cells will Types of Cancer Causing Genes  Oncogenes  Tumor suppressors Oncogenes  A mutant form of a normal gene whose presence causes cancer  Dominant - gain of function  Examples of major oncogenes include myc, ras, fos, jun, abl – key cell regulators  Overactivity mutation (gain of function) o Normal gene = proto-oncogene o A normal cell under goes a single mutation event, creating oncogene, which activates mutation enabling oncogene to stimulate cell proliferation  What types of changes can result in an oncogene? o Point mutations – slight change in the allele can cause cancer o Gene amplification – normal protein greatly overproduced  This is why everything in the cell has to be regulated at the right level o Chromosomal rearrangements  Nearby regulatory DNA sequence causes normal protein to be overproduced  Fusion to actively transcribed gene produced hyperactive fusion protein Tumor Suppressor  A gene whose absence causes cancer (recessive, loss of function)  Examples include p53 and Rb  Underactivity mutation (loss of function) o Normal cell under goes mutation event that inactivates tumor suppressor gene, having no effect of mutation in one gene copy o Second mutation event inactivates second gene copy which results in two inactivating mutations which functionally eliminate the tumor suppressor gene, stimulating cell proliferation Functions of Cancer Causi
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