1584 REDUCED PROSTATE BRANCHING MORPHOGENESIS IN STROMAL FIBROBLAST ESTROGEN RECEPTOR α KNOCKOUT, BUT NOT IN EPITHELIAL ESTROGEN RECEPTOR α KNOCKOUT MICE

Abstract

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Basic Research1 Apr 20121584 REDUCED PROSTATE BRANCHING MORPHOGENESIS IN STROMAL FIBROBLAST ESTROGEN RECEPTOR α KNOCKOUT, BUT NOT IN EPITHELIAL ESTROGEN RECEPTOR α KNOCKOUT MICE Chiuan-Ren Yeh, Ming Chen, Jun Da, Edward M. Messing, Spencer Vitkus, and Shuyuan Yeh Chiuan-Ren YehChiuan-Ren Yeh Rochester, NY More articles by this author , Ming ChenMing Chen Rochester, NY More articles by this author , Jun DaJun Da Rochester, NY More articles by this author , Edward M. MessingEdward M. Messing Rochester, NY More articles by this author , Spencer VitkusSpencer Vitkus Rochester, NY More articles by this author , and Shuyuan YehShuyuan Yeh Rochester, NY More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.1356AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Early studies using total oestrogen receptor (ER) α knockout mice demonstrated ERα is involved in prostate development. We previously reported a more complete ERα knockout mouse model by mating β-actin cre transgenic mice with floxed ERα mice (ACTB-ERαKO). These mice showed defects in prostatic branching morphogenesis and suggested ERα is necessary to maintain proliferative events in the prostate. However, within which prostatic cells ERα exerts those important functions remains to be elucidated. Therefore, it is necessary to generate specific knockout mice and evaluate the respective roles of ERα in prostate epithelial versus stromal compartments when prostate developing. METHODS We mated floxed ERα mice with either FSP-Cre or probasin-Cre transgenic mice to generate a mouse model that has deleted ERα in either stromal (FSP-ERαKO) or epithelial (pes-ERαKO) prostate cells. the mice were sacrificed and collected data at 3 month of age. Immunohistochemistry (IHC) and immunofluorescent (IF) staining were carried to stained prostate tissue sections with the following primary antibodies: anti-ERα, androgen receptor (AR), Ki67, vimentin, SM α-actin, desmin, heavy chain myosin, and pan-cytokeratin. Reverse transcription PCR also confirmed the expression of branch morphogenesis related genes as: FGF7, FGF10, IGF-1, BMP4, and BMP7. RESULTS We generated a mouse model that has selectively knockout ERα in either stromal (FSP-ERαKO) or epithelial prostate cells (pes-ERαKO) to determine the requirements of ERα for prostate development. Our results indicated that circulating testosterone and fertility were not altered in either FSP-ERαKO or pes-ERαKO male mice. FSP-ERαKO prostates have less branching morphogenesis compared to wild type littermates. Further analyses indicated that loss of stromal ERα leads to increased stromal apoptosis, reduced expression of IGF-1, and increased expression of BMP4 in FSP-EERαKO prostates. Collectively, we establish the in vivo prostate stromal and epithelial selective ERαKO mouse models and results indicating that stromal ERα indeed plays important roles in prostate development but not epithelial ERα. CONCLUSIONS The results between different in vivo ERα KO mouse models demonstrate that stromal ERα plays an important role in prostatic branching morphogenesis and prostatic homeostasis. These data also support the hypothesis that ERα regulates the prostate in the context of stromal and epithelial interaction © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e641-e642 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Chiuan-Ren Yeh Rochester, NY More articles by this author Ming Chen Rochester, NY More articles by this author Jun Da Rochester, NY More articles by this author Edward M. Messing Rochester, NY More articles by this author Spencer Vitkus Rochester, NY More articles by this author Shuyuan Yeh Rochester, NY More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...