MP62-20 CROSSTALK BETWEEN EPITHELIAL-MESENCHYMAL TRANSITION AND CASTRATION RESISTANCE IN PROSTATE CANCER (2016)

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology I1 Apr 2016MP62-20 CROSSTALK BETWEEN EPITHELIAL-MESENCHYMAL TRANSITION AND CASTRATION RESISTANCE IN PROSTATE CANCER Masaki Shiota, Momoe Itsumi, Ario Takeuchi, Kenjiro Imada, Akira Yokomizo, Hidetoshi Kuruma, Junichi Inokuchi, Katsunori Tatsugami, Takeshi Uchiumi, Yoshinao Oda, Seiji Naito, and Masatoshi Eto Masaki ShiotaMasaki Shiota More articles by this author , Momoe ItsumiMomoe Itsumi More articles by this author , Ario TakeuchiArio Takeuchi More articles by this author , Kenjiro ImadaKenjiro Imada More articles by this author , Akira YokomizoAkira Yokomizo More articles by this author , Hidetoshi KurumaHidetoshi Kuruma More articles by this author , Junichi InokuchiJunichi Inokuchi More articles by this author , Katsunori TatsugamiKatsunori Tatsugami More articles by this author , Takeshi UchiumiTakeshi Uchiumi More articles by this author , Yoshinao OdaYoshinao Oda More articles by this author , Seiji NaitoSeiji Naito More articles by this author , and Masatoshi EtoMasatoshi Eto More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.928AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Invasive and metastatic progression via the epithelial-mesenchymal transition (EMT) and acquisition of castration resistance are both critical steps in prostate cancer. However, the molecular mechanism of this interaction remains unclear. In this study, we aimed to elucidate the interaction of signaling between EMT and castration resistance, and to apply to the development of a novel therapeutic concept using transforming growth factor-ß (TGF-ß) inhibitor SB525334 combined with androgen-deprivation therapy against prostate cancer. METHODS LNCaP and 22Rv1 cells were utilized. Gene and protein expression levels were evaluated by quantitative real-time polymerase chain reaction and Western blot analysis, respectively. Protein expression in tissues was evaluated by immunohistochemistry. Cell invasion ability was examined by matrigel-invasion assay. 22Rv1 xenograft model in nude mice was utilized to investigate in vivo antitumor effect. RESULTS The results showed that TGF-ß induced full-length and variant androgen receptor (AR) expression. In addition, highly invasive clone showed augmented full-length and variant AR expression as well as acquisition of castration resistance. Conversely, full-length and variant AR as well as Twist1 and mesenchymal molecules expression were up-regulated in castration-resistant tumors (Fig. A). Actually, both full-length and variant AR expression were elevated in pT3 prostate cancer tissue, compared with pT2 tissues (Fig. B). Finally, TGF-ß inhibitor suppressed Twist1 and AR expression as well as prostate cancer growth combined with castration (Fig. C). CONCLUSIONS Taken together, these results demonstrated that Twist1/AR signaling was augmented in castration-resistant as well as mesenchymal-phenotype prostate cancer, suggesting mutual and functional crosstalk between EMT and castration resistance, which may play a crucial role in prostate cancer progression. In addition, inhibiting EMT may contribute to sustain castration sensitivity in prostate cancer. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e820-e821 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Masaki Shiota More articles by this author Momoe Itsumi More articles by this author Ario Takeuchi More articles by this author Kenjiro Imada More articles by this author Akira Yokomizo More articles by this author Hidetoshi Kuruma More articles by this author Junichi Inokuchi More articles by this author Katsunori Tatsugami More articles by this author Takeshi Uchiumi More articles by this author Yoshinao Oda More articles by this author Seiji Naito More articles by this author Masatoshi Eto More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...