Ana Caroline Hillebrand1, Lolita Schneider Pizzolato1, Gisele Branchini2, Ilma Simoni Brum3,4. 1. Laboratory of Molecular Endocrine and Tumoral Biology, Department of Physiology, Institute of Basic Sciences of Health, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, 90050-170, Brazil. 2. Department of Basic Sciences of Health, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Rio Grande do Sul, 90050-170, Brazil. 3. Laboratory of Molecular Endocrine and Tumoral Biology, Department of Physiology, Institute of Basic Sciences of Health, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, 90050-170, Brazil. ilma@ufrgs.br. 4. Laboratory of Molecular Obstetrics and Gynecology, Experimental Research Center, Department of Obstetrics and Gynecology, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, 90035-903, Brazil. ilma@ufrgs.br.
Abstract
PURPOSE: The importance of androgen receptor variants (AR-Vs) is recognized in prostate cancer. AR-Vs have been the focus of many studies. Expression of AR-Vs has been proposed as a biomarker for resistance to androgen deprivation therapy for metastatic disease. Herein, we show dynamic changes in AR-Vs expression in response to androgen modulation. METHODS: The C4-2B cell line was exposed to low (10-13 M) and high (10-8 M) androgen (dihydrotestosterone, DHT) levels, with or without flutamide. mRNA and protein expression levels were assessed by qPCR and immunohistochemistry, respectively. RESULTS: We demonstrated that high levels of DHT downregulate AR-FL and AR-Vs. Even though AR-Vs did not present ligand-binding domain, thus were not capable of binding to DHT, they present dynamic changes under androgen treatment. Treatment with flutamide alone or in association with low levels of DHT stimulates growth of prostatic cells. CONCLUSIONS: Importantly, we provide evidence that AR-Vs respond differently to androgenic modulation. These findings have implications for a better understanding of the role of AR-Vs in prostate carcinogenesis.
PURPOSE: The importance of androgen receptor variants (AR-Vs) is recognized in prostate cancer. AR-Vs have been the focus of many studies. Expression of AR-Vs has been proposed as a biomarker for resistance to androgen deprivation therapy for metastatic disease. Herein, we show dynamic changes in AR-Vs expression in response to androgen modulation. METHODS: The C4-2B cell line was exposed to low (10-13 M) and high (10-8 M) androgen (dihydrotestosterone, DHT) levels, with or without flutamide. mRNA and protein expression levels were assessed by qPCR and immunohistochemistry, respectively. RESULTS: We demonstrated that high levels of DHT downregulate AR-FL and AR-Vs. Even though AR-Vs did not present ligand-binding domain, thus were not capable of binding to DHT, they present dynamic changes under androgen treatment. Treatment with flutamide alone or in association with low levels of DHT stimulates growth of prostatic cells. CONCLUSIONS: Importantly, we provide evidence that AR-Vs respond differently to androgenic modulation. These findings have implications for a better understanding of the role of AR-Vs in prostate carcinogenesis.
Authors: Sanjay N Mediwala; Huiying Sun; Adam T Szafran; Sean M Hartig; Guru Sonpavde; Teresa G Hayes; Perumal Thiagarajan; Michael A Mancini; Marco Marcelli Journal: Prostate Date: 2012-07-20 Impact factor: 4.104
Authors: Yezi Zhu; Adam Sharp; Courtney M Anderson; John L Silberstein; Maritza Taylor; Changxue Lu; Pei Zhao; Angelo M De Marzo; Emmanuel S Antonarakis; Mindy Wang; Xingyong Wu; Yuling Luo; Nan Su; Daniel Nava Rodrigues; Ines Figueiredo; Jonathan Welti; Emily Park; Xiao-Jun Ma; Ilsa Coleman; Colm Morrissey; Stephen R Plymate; Peter S Nelson; Johann S de Bono; Jun Luo Journal: Eur Urol Date: 2017-09-01 Impact factor: 20.096
Authors: Charlie D Chen; Derek S Welsbie; Chris Tran; Sung Hee Baek; Randy Chen; Robert Vessella; Michael G Rosenfeld; Charles L Sawyers Journal: Nat Med Date: 2003-12-21 Impact factor: 53.440