Abstract 3175: Context-dependent role of ARF for response to chemotherapy in muscle invasive bladder cancer

Abstract

Abstract Muscle invasive bladder cancer (MIBC) is a significant cause of cancer death, in part because there are relatively few treatments and these have limited efficacy. Our studies show that expression of 14ARF (aka ARF), one of the major transcripts encoded by the CDKN2A tumor suppressor locus, is frequently up-regulated in MIBC, particularly in more aggressive disease subtypes. Our results further show that accumulation of ARF protein in the nucleolus is associated with poor outcome and reduced response to chemotherapy. Using both genetically-engineered mouse (GEM) models and human xenograft models of MIBC, we demonstrate that tumors expressing ARF display poor response to treatment with the platinum-based chemotherapy agent cisplatin. This is mediated in part by expression of the integrin-binding protein ITGB3BP (CENPR) and reflects ARF-dependent inhibition of protein translation, which is attenuated by drug treatment. Our findings reveal an unexpected context-dependent role for ARF in modulating drug response in bladder cancer through its ability to regulate protein translation. Citation Format: Lijie Rong, Tomasz Owczarek, Takashi Kobayashi, Cory Abate-Shen. Context-dependent role of ARF for response to chemotherapy in muscle invasive bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3175. doi:10.1158/1538-7445.AM2017-3175