1456 CENTRAL ROLE FOR PELP1-ANDROGEN RECEPTOR COMPLEX IN PROSTATE CANCER

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research1 Apr 20111456 CENTRAL ROLE FOR PELP1-ANDROGEN RECEPTOR COMPLEX IN PROSTATE CANCER Lin Yang, Preethi Ravindranath, and Ganesh Raj Lin YangLin Yang Dallas, TX More articles by this author , Preethi RavindranathPreethi Ravindranath Dallas, TX More articles by this author , and Ganesh RajGanesh Raj Dallas, TX More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1369AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Previously, we have shown that Estrogen Receptor beta (ER)β, PELP1 and Androgen Receptor (AR) can form a heterotrmeric protein complex in Prostate Cancer cells (PCa) in tissue culture. We had also shown that this protein complex plays a central role in the non-androgenic activation of AR in PCa. In this study, we examined whether ERβ, PELP1 and AR also formed a complex in vivo in both PCa cell lines, xenografts and human PCa tumors. METHODS Extracts from a large variety of PCa cell lines were prepared and evaluated by immunohistochemistry (IHC) and by co-immunoprecipitations (CO-IPs) for the presence of the heterotrimeric complex following treatment with estradiol (E2) or dihydrotestosterone (DHT). Then, following subcutaneously injection of Androgen-independent C4-2 Pca cells into 12 male nude mice and establishment of tumors, six mice were subject to surgical castration. Tumor samples from these mice were then harvested and extracts prepared to examine the formation of the trimeric complex before and after castration by IHC and CO-IP. In addition, fifty-eight samples from androgen dependent (ADPCa) and androgen independent human PCa (AIPCa) were screened for ERβ, PELP1 and AR expression by IHC and complex formation by CO-IP. RESULTS The complex between ERβ, PELP1 and AR was consistently detected in all PCa cell lines with AR. Treatment with DHT or E2 increased the detectability of the complex. In those PCa cell lines without AR, introduction of AR by transient or stable transfection restored the trimeric complex. The heterotrimeric complex between ERβ, PELP1 and AR was consistently detected PCa tumor samples from xenograft mice. Castration did not appear to significantly affect the detection of this trimeric complex in xenograft mice. In the human PCa tissue, PELP1 expression was increased significantly in AIPCa, while AR and ERβ expression was slightly decreased. Interestingly, while the complex between AR and PELP1 was detectable in both ADPCa and AIPCa samples, the level of the complex was significantly upregulated in AIPCa samples. CONCLUSIONS These data suggest that ERβ, PELP1 and AR form a heterotrimeric protein complex in PCa cells in vivo. This complex is present in all PCa cells with an intact AR. The complex appears to be upregulated up on androgenic and non-androgenic activation and in AIPCa Coupled with previous observations about the functional importance of this complex, these data appear to validate our approach to design agents targeting the formation of this complex. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e584 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Lin Yang Dallas, TX More articles by this author Preethi Ravindranath Dallas, TX More articles by this author Ganesh Raj Dallas, TX More articles by this author Expand All Advertisement Advertisement Loading ...