Abstract
Abstract The mechanism regulating radiation-induced anti-apoptotic response in prostate cancer cell lines is not clear yet. Wip1 is the major member of the Ser/Thr PP2C family that dephosphorylates and inactivates p38 MAPK, p53, chk1, Mdm2 and ATM. Here we provide Wip1 was negative regulator of γ-radiation-mediated apoptotic response in LNCaP cells. The levels of Wip1 were increased after exposed to γ-radiation and induced Wip1 repressed cell death. Wip1 depletion with siRNA resulted in increased apoptotic cell death in LNCaP cells, which was not observed in radiation-sensitive HeLa cells. Radiation-induced Wip1 induction was inversely co-related with the decrease of phospho-JNK and -p38 MAPK in LNCaP cells, indicating that Wip1 is a negative regulator of JNK and p38 MAPK pathways. Furthermore, in response to γ-radiation, Bax proteins are increased and directly interact with Wip1. The data suggest that Wip1 may be a central player on the mechanism of radio-resistance in LNCaP cells. Currently, we are investigating the role of Wip1 in BAX-mediated apoptotic cell death. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3839. doi:10.1158/1538-7445.AM2011-3839
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