174 DIHYDROTESTOSTERONE ENHANCES RENAL CELL CARCINOMA CELL SURVIVAL THROUGH SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION-5 ACTIVATION VIA ANDROGEN RECEPTOR AND/OR GLUCOCORTICOID RECEPTOR

Abstract

You have accessJournal of UrologyKidney Cancer: Basic Research (I)1 Apr 2013174 DIHYDROTESTOSTERONE ENHANCES RENAL CELL CARCINOMA CELL SURVIVAL THROUGH SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION-5 ACTIVATION VIA ANDROGEN RECEPTOR AND/OR GLUCOCORTICOID RECEPTOR Yunlim Kim, Wansuk Kim, Sejun Park, Myungsun Shim, Dalsan You, Cheryn Song, and Hanjong Ahn Yunlim KimYunlim Kim Seoul, Korea, Republic of More articles by this author , Wansuk KimWansuk Kim Busan, Korea, Republic of More articles by this author , Sejun ParkSejun Park Seoul, Korea, Republic of More articles by this author , Myungsun ShimMyungsun Shim Seoul, Korea, Republic of More articles by this author , Dalsan YouDalsan You Seoul, Korea, Republic of More articles by this author , Cheryn SongCheryn Song Seoul, Korea, Republic of More articles by this author , and Hanjong AhnHanjong Ahn Seoul, Korea, Republic of More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.1554AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Androgen receptor (AR) and glucocorticoid receptor (GR) mediate the action of steroid hormones in various tissues, including the kidney. Signal transducer and activator of transcription-5 (STAT5) regulates the expression of genes that mediate cell survival, proliferation, and angiogenesis and is activated in various types of malignancies, including renal cell carcinoma (RCC). Although several important transcriptional targets of STAT5 are known, the effect and molecular mechanism of STAT5 are not well elucidated, especially in RCC cells. Therefore, we examined interaction between STAT5 activation and steroid receptor in RCC. METHODS Using clear cell RCC cell lines Caki-2, A498 and SN12C cell viability assay and Western blot for phosphorylated STAT5 was done after dihydrotestosterone (DHT) treatment at various concentration (0.1, 1, 10nM). Endogenous levels of AR, GR and estrogen receptor (ER) were identified by RT-PCR and Western blot. Using AR antagonist (bicalutamide)/GR antagonist (RU486) and AR/GR-specific siRNA, changes in DHT-induced STAT5 activation were assessed. In human primary RCC cells from patients, cell viability and STAT5 activation after treatment of DHT was assessed by Western blot. RESULTS DHT treatment enhanced STAT5 phosphorylation and promoted cell proliferation up to 34.3% in Caki-2, 25.0% in A498 and 15.7% in SN12C, respectively. Endogenous AR was identified strongly in Caki-2 (193 fold relative to SN12C), weakly in A498 (54 fold relative to SN12C), but not in SN12C. GR was identified strongly in A498, weakly in Caki-2 (0.55 fold relative to A498) and SN12C (0.68 fold relative to A498). Pretreatment of bicalutamide/RU486 abolished DHT-induced cell proliferation and STAT5 activation in these cell lines. Similarly, AR/GR-specific siRNA completely suppressed DHT-induced STAT5 activation. In addition, DHT enhanced cell proliferation and STAT5 activation in 75% of human primary RCC cells expressing AR and/or GR. CONCLUSIONS In RCC cells, DHT activated STAT5 enhancing cell survival and proliferation through STAT5 via AR and/or GR. AR and GR may be new therapeutic target in RCC. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e71 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yunlim Kim Seoul, Korea, Republic of More articles by this author Wansuk Kim Busan, Korea, Republic of More articles by this author Sejun Park Seoul, Korea, Republic of More articles by this author Myungsun Shim Seoul, Korea, Republic of More articles by this author Dalsan You Seoul, Korea, Republic of More articles by this author Cheryn Song Seoul, Korea, Republic of More articles by this author Hanjong Ahn Seoul, Korea, Republic of More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...