TR4 nuclear receptor enhances prostate cancer initiation via altering the stem cell population and EMT signals in the PPARG-deleted prostate cells
Abstract | PDF | Full Text | Supplementary Materials | How to Cite
https://doi.org/10.18632/oncoscience.121
Shin-Jen Lin1, Dong-Rong Yang1,2, Nancy Wang1, Ming Jiang3, Hiroshi Miyamoto1, Gonghui Li1,4 and Chawnshang Chang1,5
1 George Whipple Lab for Cancer Research, Departments of Pathology, Urology, Radiation Oncology, and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY, USA
2 Department of Urology, the Second Affiliated Hospital of Suzhou University, Suzhou, China
3 Department of Urologic Surgery, Vanderbilt-Ingram Comprehensive Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA
4 Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China
5 Sex Hormone Research Center, China Medical University/Hospital, Taichung, Taiwan
Correspondence:
Chawnshang Chang, email:
Gonghui Li, email:
Keywords: Prostate cancer, TR4, PPARG
Received: August 05, 2014 Accepted: Febraury 06, 2015 Published: Febraury 09, 2015
Abstract
A recent report indicated that the TR4 nuclear receptor might suppress the prostate cancer (PCa) initiation via modulating the DNA damage/repair system. Knocking-out peroxisome proliferator-activated receptor gamma (PPARG), a nuclear receptor that shares similar ligands/activators with TR4, promoted PCa initiation. Here we found 9% of PCa patients have one allele of PPARG deletion. Results from in vitro cell lines and in vivo mouse model indicated that during PCa initiation TR4 roles might switch from suppressor to enhancer in prostate cells when PPARG was deleted or suppressed (by antagonist GW9662). Mechanism dissection found targeting TR4 in the absence of PPARG might alter the stem cell population and epithelial-mesenchymal transition (EMT) signals. Together, these results suggest that whether TR4 can enhance or suppress PCa initiation may depend on the availability of PPARG and future potential therapy via targeting PPARG to battle PPARG-related diseases may need to consider the potential side effects of TR4 switched roles during the PCa initiation.
