Genomic Activation of <i>PPARG</i> Reveals a Candidate Therapeutic Axis in Bladder Cancer.

Goldstein, Jonathan T; Berger, Ashton C; Shih, Juliann; Duke, Fujiko F; Furst, Laura; Kwiatkowski, David J; Cherniack, Andrew D; Meyerson, Matthew et al. · Cancer Res · 2017

basic_science · Level V

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Abstract

The <i>PPARG</i> gene encoding the nuclear receptor PPARγ is activated in bladder cancer, either directly by gene amplification or mutation, or indirectly by mutation of the <i>RXRA</i> gene, which encodes the heterodimeric partner of PPARγ. Here, we show that activating alterations of <i>PPARG</i> or <i>RXRA</i> lead to a specific gene expression signature in bladder cancers. Reducing PPARG activity, whether by pharmacologic inhibition or genetic ablation, inhibited proliferation of PPARG-activated bladder cancer cells. Our results offer a preclinical proof of concept for PPARG as a candidate therapeutic target in bladder cancer. <i>Cancer Res; 77(24); 6987-98. ©2017 AACR</i>.

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