机构：[1]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[2]Department of Urology, The Second Affiliated Hospital of Soochow University, Suzhou, China[3]Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China[4]Sex Hormone Research Center, China Medical University/Hospital, Taichung, Taiwan
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.
基金：
This work was supported by the National Institutes of Health grants (CA156700 and
DK73414) and by Taiwan Ministry ofHealth and Welfare Clinical Trial and Research Center
of Excellence (MOHW104-TDU-B-212-113002).
第一作者机构：[1]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
通讯作者：
通讯机构：[1]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[3]Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China[4]Sex Hormone Research Center, China Medical University/Hospital, Taichung, Taiwan
推荐引用方式(GB/T 7714)：
Shin-Jen Lin,Chang-Yi Lin,Dong-Rong Yang,et al.The Differential Effects of Anti-Diabetic Thiazolidinedione on Prostate Cancer Progression Are Linked to the TR4 Nuclear Receptor Expression Status[J].NEOPLASIA.2015,17(4):339-47.doi:10.1016/j.neo.2015.02.005.
APA：
Shin-Jen Lin,Chang-Yi Lin,Dong-Rong Yang,Kouji Izumi,Emily Yan...&ChawnshangChang.(2015).The Differential Effects of Anti-Diabetic Thiazolidinedione on Prostate Cancer Progression Are Linked to the TR4 Nuclear Receptor Expression Status.NEOPLASIA,17,(4)
MLA：
Shin-Jen Lin,et al."The Differential Effects of Anti-Diabetic Thiazolidinedione on Prostate Cancer Progression Are Linked to the TR4 Nuclear Receptor Expression Status".NEOPLASIA 17..4(2015):339-47
