MP84-03 EXPRESSION OF ANDROGEN RECEPTOR SPLICE VARIANTS IN A NOVEL CASTRATION RESISTANT PROSTATE CANCER XENOGRAFT MODEL

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology III1 Apr 2016MP84-03 EXPRESSION OF ANDROGEN RECEPTOR SPLICE VARIANTS IN A NOVEL CASTRATION RESISTANT PROSTATE CANCER XENOGRAFT MODEL Takahiro Kimura, Mariko Honda, Kojiro Tashiro, Shigehiro Bando, Hiroshi Sasaki, Yuko Kamata, Jun Miki, and Shin Egawa Takahiro KimuraTakahiro Kimura More articles by this author , Mariko HondaMariko Honda More articles by this author , Kojiro TashiroKojiro Tashiro More articles by this author , Shigehiro BandoShigehiro Bando More articles by this author , Hiroshi SasakiHiroshi Sasaki More articles by this author , Yuko KamataYuko Kamata More articles by this author , Jun MikiJun Miki More articles by this author , and Shin EgawaShin Egawa More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2227AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Androgen receptor (AR) splice variants have been reported as key players in the development of castration resistant prostate cancer (PCa). AR splice variant 7 (AR-V7) is a form of them encoding a truncated AR protein that lacks the ligand-binding domain and remains constitutively active as a transcription factor without androgen. AR-V7 in circulating tumor cells from patients with metastatic castration-resistant PCa was recently demonstrated to be associated with resistance to abiraterone and enzalutamide. We have established a mouse xenograft model, JDCaP, from skin metastatic tissue of Japanese castration resistant PCa patient which was revealed to have androgen sensitivity (Kimura T, et al. Prostate. 2009;69:1660). In the present study, we established castration resistant sublines, JDCaP-HR, from JDCaP and analyzed the sequence and expression profile of molecules including full length AR and AR splice variants using whole transcriptome sequencing. METHODS JDCaP was transplanted to female or castrated male nude mice and the stable castration resistant sublines, JDCaP-HR 1, 2, 3 and 4, were established by serial passages. Whole transcriptome analysis by next-generation sequencing was performed to analyze the sequence and expression profile of molecules including full length AR and AR splice variants in these cells. RESULTS Administration of bicalutamide did not show any anti-tumor effect for all of the established JDCaP-HRs and their castration resistance was confirmed. Whole transcriptome analysis revealed that 49 genes were up-regulated and 14 genes were down-regulated in JDCaP-HR comparing to JDCaP. The expression of wild type-AR was significantly higher in JDCaP-HRs than in JDCaP (Figure). In addition, three of JDCaP-HRs expressed AR-V7 and the other subline expressed another form of truncated AR splice variant, ARV567es which was also deleted the ligand-binding domain. The parental JDCaP did not express any AR splice variants. CONCLUSIONS All castration resistant sublines expressed the truncated forms of AR splice variants. The results suggest that AR splice variants may have an important role in development of castration resistance in PCa. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e1090 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Takahiro Kimura More articles by this author Mariko Honda More articles by this author Kojiro Tashiro More articles by this author Shigehiro Bando More articles by this author Hiroshi Sasaki More articles by this author Yuko Kamata More articles by this author Jun Miki More articles by this author Shin Egawa More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...