PMID- 25925376 OWN - NLM STAT- MEDLINE DCOM- 20160120 LR - 20181113 IS - 1476-5586 (Electronic) IS - 1522-8002 (Print) IS - 1476-5586 (Linking) VI - 17 IP - 4 DP - 2015 Apr TI - The Differential Effects of Anti-Diabetic Thiazolidinedione on Prostate Cancer Progression Are Linked to the TR4 Nuclear Receptor Expression Status. PG - 339-47 LID - S1476-5586(15)00031-7 [pii] LID - 10.1016/j.neo.2015.02.005 [doi] AB - The insulin sensitizers, thiazolidinediones (TZDs), have been used as anti-diabetic drugs since the discovery of their ability to alter insulin resistance through transactivation of peroxisome proliferator-activated receptors (PPARs). However, their side effects in hepatitis, cardiovascular diseases, and bladder cancer resulted in some selling restrictions in the USA and Europe. Here, we found that the potential impact of TZDs on the prostate cancer (PCa) progression might be linked to the TR4 nuclear receptor expression. Clinical surveys found that 9% of PCa patients had one allele TR4 deletion in their tumors. TZD increased cell growth and invasion in PCa cells when TR4 was knocked down. In contrast, TZD decreased PCa progression in PCa cells with wild type TR4. Mechanism dissection found that the Harvey Rat Sarcoma (HRAS) oncogene increased on TZD treatment of the TR4 knocked-down CWR22Rv1 and C4-2 cells, and interruption with HRAS inhibitor resulted in reversal of TZD-induced PCa progression. Together, these results suggest that TZD treatment may promote PCa progression depending on the TR4 expression status that may be clinically relevant since extra caution may be needed for those diabetic PCa patients receiving TZD treatment who have one allele TR4 deletion. CI - Copyright (c) 2015 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Lin, Shin-Jen AU - Lin SJ AD - The 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. FAU - Lin, Chang-Yi AU - Lin CY AD - The 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. FAU - Yang, Dong-Rong AU - Yang DR AD - The 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; Department of Urology, The Second Affiliated Hospital of Soochow University, Suzhou, China. FAU - Izumi, Kouji AU - Izumi K AD - The 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. FAU - Yan, Emily AU - Yan E AD - The 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. FAU - Niu, Xiaodan AU - Niu X AD - The 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. FAU - Chang, Hong-Chiang AU - Chang HC AD - The 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. FAU - Miyamoto, Hiroshi AU - Miyamoto H AD - The 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. FAU - Wang, Nancy AU - Wang N AD - The 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. FAU - Li, Gonghui AU - Li G AD - The 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; Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China. Electronic address: ligonghui1970@hotmail.com. FAU - Chang, Chawnshang AU - Chang C AD - The 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; Sex Hormone Research Center, China Medical University/Hospital, Taichung, Taiwan. Electronic address: chang@urmc.rochester.edu. LA - eng GR - R01 CA156700/CA/NCI NIH HHS/United States GR - R01 DK073414/DK/NIDDK NIH HHS/United States GR - CA156700/CA/NCI NIH HHS/United States GR - DK73414/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Neoplasia JT - Neoplasia (New York, N.Y.) JID - 100886622 RN - 0 (Antidiuretic Agents) RN - 0 (NR2C2 protein, human) RN - 0 (Receptors, Steroid) RN - 0 (Receptors, Thyroid Hormone) RN - 0 (Thiazolidinediones) RN - EC 3.6.5.2 (HRAS protein, human) RN - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras)) SB - IM MH - Alleles MH - Animals MH - Antidiuretic Agents/*pharmacology MH - Cell Line, Tumor MH - Cell Proliferation/drug effects/genetics MH - Disease Progression MH - Humans MH - Male MH - Mice MH - Mice, Nude MH - Neoplasm Invasiveness/genetics/pathology MH - Prostatic Neoplasms/*drug therapy/*genetics/pathology MH - Proto-Oncogene Proteins p21(ras)/genetics MH - Receptors, Steroid/*genetics MH - Receptors, Thyroid Hormone/*genetics MH - Thiazolidinediones/*pharmacology PMC - PMC4415117 EDAT- 2015/05/01 06:00 MHDA- 2016/01/21 06:00 PMCR- 2015/04/26 CRDT- 2015/05/01 06:00 PHST- 2014/12/24 00:00 [received] PHST- 2015/02/17 00:00 [revised] PHST- 2015/02/27 00:00 [accepted] PHST- 2015/05/01 06:00 [entrez] PHST- 2015/05/01 06:00 [pubmed] PHST- 2016/01/21 06:00 [medline] PHST- 2015/04/26 00:00 [pmc-release] AID - S1476-5586(15)00031-7 [pii] AID - 10.1016/j.neo.2015.02.005 [doi] PST - ppublish SO - Neoplasia. 2015 Apr;17(4):339-47. doi: 10.1016/j.neo.2015.02.005.