| Literature DB >> 28082400 |
Tomasz B Owczarek1,2, Takashi Kobayashi2, Ricardo Ramirez3,4, Lijie Rong1,2, Anna M Puzio-Kuter2, Gopa Iyer5,6, Min Yuen Teo5, Francisco Sánchez-Vega7,8, Jingqiang Wang2, Nikolaus Schultz7,8, Tian Zheng9, David B Solit3,5,8,6, Hikmat A Al-Ahmadie10, Cory Abate-Shen11,2,12,13,14,15.
Abstract
Muscle-invasive bladder cancer (MIBC) generally responds poorly to treatment and tends to exhibit significant mortality. Here we show that expression of the tumor suppressor p14ARF (ARF) is upregulated in aggressive subtypes of MIBC. Accumulation of ARF in the nucleolus is associated with poor outcome and attenuated response to chemotherapy. In both genetically engineered mouse models and murine xenograft models of human MIBC, we demonstrate that tumors expressing ARF failed to respond to treatment with the platinum-based chemotherapy agent cisplatin. Resistance was mediated in part by the integrin-binding protein ITGB3BP (CENPR) and reflected ARF-dependent impairment of protein translation, which was exaggerated by drug treatment. Overall, our results highlight a context-dependent role for ARF in modulating the drug response of bladder cancer. Cancer Res; 77(4); 1035-46. ©2017 AACR. ©2017 American Association for Cancer Research.Entities:
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Year: 2017 PMID： 28082400 PMCID： PMC5313321 DOI： 10.1158/0008-5472.CAN-16-2621
Source DB: PubMed Journal: Cancer Res ISSN： 0008-5472 Impact factor: 12.701