Wild-type and mutant p53 mediate cisplatin resistance through interaction and inhibition of active caspase-9.

ABSTRACT: The p53 gene has been implicated in many cancers due to its frequent mutations as well as mutations in other genes whose proteins directly affect p53's functions. In addition, high expression of p53 [wild-type (WT) or mutant] has been found in the cytoplasm of many tumor cells, and studies have associated these observations with more aggressive tumors and poor prognosis. Cytoplasmic mis-localization of p53 subsequently reduced its transcriptional activity and this loss-of-function (LOF) was used to explain the lack of response to chemotherapeutic agents. However, this hypothesis seemed inadequate in explaining the apparent selection for tumor cells with high levels of p53 protein, a phenomenon that suggests a gain-of-function (GOF) of these mis-localized p53 proteins. In this study, we exp

SUBMITTER: Chee JL 

PROVIDER: S-EPMC3575457 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature