A subset of muscle-invasive bladder cancer (BLCA) is typified by PPARG pathway activation. PPARG focal gene amplification occurs in 15% of bladder cancer patients, and similarly, 5% of BLCA patients possess hotspot mutations in the requisite heterodimer partner of PPARG, RXRA (S427F, S427Y). We used genetic perturbation to study the role of PPARG in bladder cancer. Our results show that overexpression of RXRA and PPARG mutant alleles activate expression of PPARG and PPARA target genes in a ligand-independent manner, and that bladder cancer cell lines are dependent on PPARG for viability. These findings suggest that PPARG may be a promising therapeutic target for treatment of bladder cancer.

Citation Format: Jonathan T. Goldstein, Craig Strathdee, Fujiko Duke, Juliann Shih, Matthew Meyerson. Validation of PPARG and RXRA as drivers of 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 3627. doi:10.1158/1538-7445.AM2017-3627