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The Role of Mutant p53 Protein in Breast Cancer.

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Mutation of the p53 gene is very frequent in breast cancer. In normal cells induction od wild-type p53 function leads to either cell cycle arrest or cell death. Loss of this function can contribute to oncogenic cell transformation. Additionally the presence of mutant forms of p53 in breast tumor cells may actually facilitate the process of tumorigenesis. The properties of mutant pS3 proteins in vitro and in breast tumor cell lines will be studied. Experiments will focus on analysis of the structure and modification of mutant p53 proteins as well as the effect of cellular signalling on p53 function. Additionally it is planned to establish breast cell lines expressing inducible mutant p53 to determine the effect of such mutants on parameters of cell cycle, growth and death. We have discovered that all mutant forms of p53 tested are capable of binding specifically to p53 response elements present in p53 target genes at lower but not at physiological temperatures. Furthermore we have identified a means by which such binding is stabilized at the higher temperature. This will allow us to explore means to develop molecules that might have the outcome of converting p53 in breast tumor cells from mutant to wild-type in function. Such reagents would have clear therapeutic advantages.

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  • Medicine and Medical Research
  • Genetic Engineering and Molecular Biology

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