Abstract SY14-02: p53-mediated senescence impairs the apoptotic response to chemotherapy in breast cancer

Abstract

Abstract Studies on the role of p53 mutation in human breast cancer response to chemotherapy are controversial. Using MMTV-Wnt1 murine breast tumor model, we show that tumors with mutant p53 exhibited a superior clinical response compared to tumors with wild-type p53. Doxorubicin treated p53-mutant tumors failed to arrest proliferation leading to abnormal mitoses and cell death, while p53 wild-type tumors underwent arrest and senescence with expression of senescence-associated cytokines that led to autocrine/paracrine activity and mitogenic potential. Wild-type p53 could still mediate arrest and inhibit drug response even in the context of a heterozygous p53 point mutation or absence of p21. Thus, we show wild-type p53 activity hinders chemotherapy response and demonstrate the need to reassess the paradigm for p53 in cancer therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr SY14-02. doi:1538-7445.AM2012-SY14-02