Role of Mutant p53 Protein in Breast Cancer

摘要

Mutation of the p53 gene is very frequent in breast cancer. In normal cells induction of 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 p53 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 signaling 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.