Genomic Activation of PPARG Reveals a Candidate Therapeutic Axis in Bladder Cancer

December 15, 2017

Assays were performed by seeding 384-well plates with 10,000 cells per well in MEMalpha containing 10% FBS and dosing compounds at indicated concentration using the HP D300 digital dispenser (HP/Tecan)

The PPARG gene encoding the nuclear receptor PPARγ is activated in bladder cancer, either directly by gene amplification or mutation, or indirectly by mutation of the RXRA gene, which encodes the heterodimeric partner of PPARγ. Here, we show that activating alterations of PPARG or RXRA 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. Cancer Res; 77(24); 6987-98. Š2017 AACR. Š2017 American Association for Cancer Research.

Goldstein, JT; Berger, AC; Shih, J; Duke, FF; Furst, L; Kwiatkowski, DJ; Cherniack, AD; Meyerson, M; Strathdee, CA;

Journal: Cancer Res. Pages: 6987-6998

Original article (28923856)