ARF confers a context-dependent response to chemotherapy in muscle-invasive bladder cancer Academic Article uri icon

Overview

MeSH Major

  • Tumor Suppressor Protein p14ARF
  • Urinary Bladder Neoplasms

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 p14(ARF) (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.

publication date

  • February 15, 2017

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC5313321

Digital Object Identifier (DOI)

  • 10.1158/0008-5472.CAN-16-2621

PubMed ID

  • 28082400

Additional Document Info

start page

  • 1035

end page

  • 1046

volume

  • 77

number

  • 4