Mutant p53 accumulation in human breast cancer is not an intrinsic property or dependent on structural or functional disruption but is regulated by exogenous stress and receptor status

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It has been something of a mystery that mutant p53 (caused by mis-sense mutations) can be detected immunohistochemically by the presence of large amounts of stabilized p53 protein. We wanted to investigate why this should be so. We looked at whether specific mutations (in terms of the physico-chemical properties of the mutant protein) influenced stability and found this was not the case in primary human cancers and human cancer cell lines. However, agents that stabilize wild-type p53 also stabilized mutant p53. In human breast cancer samples, there was a correlation between p53 stabilization and the specific tumour sub-type, and an inverse correlation with the level of MDM2. The data show that human cancers are responsible for regulating p53 mutant stability and that this oncogenic protein could be enhanced by certain treatments, although there is also now the possibility to reduce mutant p53 activity as a therapy for human cancer.

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