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

Cancer Res. 2017 Dec 15;77(24):6987-6998. doi: 10.1158/0008-5472.CAN-17-1701. Epub 2017 Sep 18.


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. ©2017 AACR.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CRISPR-Cas Systems
  • Cell Line, Tumor
  • Gene Amplification / physiology
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Microarray Analysis
  • Molecular Targeted Therapy*
  • Mutation / physiology
  • PPAR gamma / genetics*
  • Transcriptome / physiology
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / therapy*


  • PPAR gamma