The Role of Tim50 in Chemoresistance and Oncogenesis of Breast Cancer
Annual summary 1 Sep 2009-31 Aug 2010
VIRGINIA COMMONWEALTH UNIV RICHMOND
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To investigate how gain of function p53 mutants exert their oncogenic effects, protein expression was compared between a p53 null cell line stably expressing vector alone or the p53 gain of function mutants, p53-R175H and -R273H. One protein that was upregulated in cells expressing the p53 gain of function mutants control cell lines was identified by mass spectrometry as translocator of the mitochondrial membrane 50 Tim50. p53-R175H and -R273H, but not WT p53, upregulated the luciferase activity of a Tim50 promoter construct. Loss of Tim50 expression also reduced the growth rate and survival from paclitaxel treatment in breast cancer cells that harbor p53-175H. Taken together, this data suggests that one pathway by which mutant p53 may upregulated cell growth and chemoresistance in breast cancer is through induction of Tim50 protein.
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- Medicine and Medical Research