558 ANDROGEN ACTIVATES β-CATENIN SIGNALING IN ANDROGEN RECEPTOR-POSITIVE BLADDER CANCER CELLS

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research I1 Apr 2012558 ANDROGEN ACTIVATES β-CATENIN SIGNALING IN ANDROGEN RECEPTOR-POSITIVE BLADDER CANCER CELLS Yi Li, Yichun Zheng, Koji Izumi, Bo Ye, Faqian Li, and Hiroshi Miyamoto Yi LiYi Li Rochester, NY More articles by this author , Yichun ZhengYichun Zheng Rochester, NY More articles by this author , Koji IzumiKoji Izumi Rochester, NY More articles by this author , Bo YeBo Ye Rochester, NY More articles by this author , Faqian LiFaqian Li Rochester, NY More articles by this author , and Hiroshi MiyamotoHiroshi Miyamoto Rochester, NY More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.633AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Androgen receptor (AR) signals play an important role in bladder carcinogenesis and tumor progression. Activation of Wnt/β-catenin signaling has also been reported to correlate with poor prognosis in bladder cancer patients. However, cross-talk between AR and β-catenin pathways in bladder cancer remains unknown. METHODS We performed western blotting to assess the expression of total β-catenin (TBC), an active form of β-catenin (ABC), and its downstream targets in human urothelial carcinoma cell lines, including AR-positive UMUC3 and AR-negative 5637 and J82 (with or without stable expression of AR), following treatment with dihydrotestosterone (DHT) and/or an anti-androgen hydroxyflutamide (HF). We also performed immunohistochemistry to determine expression levels of β-catenin (as well as AR) and its localization in human bladder cancer tissues. RESULTS In AR-positive bladder cancer cells, DHT increased the expression of ABC over mock treatment and HF at least partially blocked the effect of DHT. DHT also slightly augmented TBC levels in these cells. DHT enhanced nuclear expression of β-catenin (TBC and ABC) in 5637-AR and J82-AR, but not in 5637 and J82. In addition, DHT up-regulated the expression of downstream of β-catenin, c-myc and epidermal growth factor receptor, in the AR-positive cells, but not in their parental AR-negative cells. In 24 radical cystectomy specimens, β-catenin was expressed in all non-neoplastic urothelial tissues, while the signals were weaker or lost in 62% of cancer tissues (p=0.0015). Loss of membrane/cytosol β-catenin signals was strongly associated with muscle-invasion (≥pT2) (p=0.0474). Interestingly, there was a strong relationship between nuclear AR expression and nuclear β-catenin expression (p=0.0215). Kaplan-Meier and log-rank tests further revealed that loss of β-catenin expression in membrane/cytosol significantly correlated with poorer prognosis (p=0.0326). Furthermore, co-expression of nuclear AR/β-catenin (p=0.0010), but not nuclear β-catenin expression alone (p=0.2424), correlated with tumor progression. CONCLUSIONS Our results suggest that androgen activates β-catenin signaling via the AR pathway in bladder cancer cells. Co-expression of AR and β-catenin in bladder cancer likely predicts poor prognosis. AR signals may thus contribute to the progression of bladder cancer via regulation of the Wnt/β-catenin pathway. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e228 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yi Li Rochester, NY More articles by this author Yichun Zheng Rochester, NY More articles by this author Koji Izumi Rochester, NY More articles by this author Bo Ye Rochester, NY More articles by this author Faqian Li Rochester, NY More articles by this author Hiroshi Miyamoto Rochester, NY More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...