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- W2068228017 abstract "No AccessJournal of UrologyInvestigative Urology1 Sep 2012Mifepristone Inhibits GRβ Coupled Prostate Cancer Cell Proliferation Martin Ligr, Yirong Li, Susan K. Logan, Samir Taneja, Jonathan Melamed, Hebert Lepor, Michael J. Garabedian, and Peng Lee Martin LigrMartin Ligr Department of Pathology, New York University Cancer Institute, New York, New York Department of Medicine, New York University Cancer Institute, New York, New York More articles by this author , Yirong LiYirong Li Department of Pathology, New York University Cancer Institute, New York, New York More articles by this author , Susan K. LoganSusan K. Logan Department of Urology, New York University Cancer Institute, New York, New York Department of Pharmacology, New York University Cancer Institute, New York, New York New York University Cancer Institute, New York University Cancer Institute, New York, New York More articles by this author , Samir TanejaSamir Taneja Department of Urology, New York University Cancer Institute, New York, New York New York University Cancer Institute, New York University Cancer Institute, New York, New York Financial interest and/or other relationship with Eigen, GTX, Janssen, Histoscanning and Steba Biotech. More articles by this author , Jonathan MelamedJonathan Melamed Department of Pathology, New York University Cancer Institute, New York, New York More articles by this author , Hebert LeporHebert Lepor Department of Urology, New York University Cancer Institute, New York, New York New York University Cancer Institute, New York University Cancer Institute, New York, New York More articles by this author , Michael J. GarabedianMichael J. Garabedian Department of Urology, New York University Cancer Institute, New York, New York Department of Microbiology, New York University Cancer Institute, New York, New York New York University Cancer Institute, New York University Cancer Institute, New York, New York More articles by this author , and Peng LeePeng Lee Department of Pathology, New York University Cancer Institute, New York, New York Department of Urology, New York University Cancer Institute, New York, New York New York University Cancer Institute, New York University Cancer Institute, New York, New York New York University School of Medicine and New York Harbor Healthcare System, New York, New York More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.04.102AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: The GR gene produces GRα and GRβ isoforms by alternative splicing of a C-terminal exon. GRα binds glucocorticoids, modulates transcription in a glucocorticoid dependent manner and has a growth inhibitory role in prostate cells. Due to this role glucocorticoids are often used to treat androgen independent prostate cancer. In contrast, GRβ has intrinsic transcriptional activity and binds mifepristone (RU486) but not glucocorticoids to control gene expression. To our knowledge the role of GRβ in prostate cell proliferation is unknown. Materials and Methods: We determined GRβ levels in various prostate cancer cell lines by reverse transcriptase-polymerase chain reaction and Western blot. The effect of GRβ on the kinetics of prostate cancer cell growth was determined by cell counting and flow cytometry upon mifepristone and dexamethasone treatment. Cell proliferation was also examined after siRNA mediated knockdown and over expression of GRβ. Results: GRβ mRNA and protein were up-regulated in LNCaP cells that over expressed the androgen receptor co-factor ARA70β. Treatment of LNCaP-ARA70β with mifepristone or siRNA targeting GRβ inhibited proliferation compared to that of parental LNCaP cells. The immortal but nontumorigenic RC165 prostate cell line and the tumorigenic DU145 prostate cell line with endogenous GRβ also showed partial growth reduction upon GRβ depletion but to a lesser extent than LNCaP-ARA70β cells. The growth stimulatory effect of ARA70β on LNCaP cells was partly GRβ dependent, as was the proliferation of RC165 cells and to a lesser extent of DU145 cells. Conclusions: Results suggest that patients with a primary tumor that expresses GRβ and ARA70β may benefit from mifepristone. References 1 : The biology of hormone refractory prostate cancer: Why does it develop?. Urol Clin North Am1999; 26: 263. Google Scholar 2 : Glucocorticoid receptor signaling and prostate cancer. Cancer Lett2011; 302: 1. Google Scholar 3 : Glucocorticoids and treatment of prostate cancer: a preclinical and clinical review. Urology2002; 60: 553. 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Volume 188Issue 3September 2012Page: 981-988 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.Keywordsmifepristonegene expressionprostateprostatic neoplasmsreceptorsglucocorticoidMetricsAuthor Information Martin Ligr Department of Pathology, New York University Cancer Institute, New York, New York Department of Medicine, New York University Cancer Institute, New York, New York More articles by this author Yirong Li Department of Pathology, New York University Cancer Institute, New York, New York More articles by this author Susan K. Logan Department of Urology, New York University Cancer Institute, New York, New York Department of Pharmacology, New York University Cancer Institute, New York, New York New York University Cancer Institute, New York University Cancer Institute, New York, New York More articles by this author Samir Taneja Department of Urology, New York University Cancer Institute, New York, New York New York University Cancer Institute, New York University Cancer Institute, New York, New York Financial interest and/or other relationship with Eigen, GTX, Janssen, Histoscanning and Steba Biotech. More articles by this author Jonathan Melamed Department of Pathology, New York University Cancer Institute, New York, New York More articles by this author Hebert Lepor Department of Urology, New York University Cancer Institute, New York, New York New York University Cancer Institute, New York University Cancer Institute, New York, New York More articles by this author Michael J. Garabedian Department of Urology, New York University Cancer Institute, New York, New York Department of Microbiology, New York University Cancer Institute, New York, New York New York University Cancer Institute, New York University Cancer Institute, New York, New York More articles by this author Peng Lee Department of Pathology, New York University Cancer Institute, New York, New York Department of Urology, New York University Cancer Institute, New York, New York New York University Cancer Institute, New York University Cancer Institute, New York, New York New York University School of Medicine and New York Harbor Healthcare System, New York, New York More articles by this author Expand All Advertisement PDF downloadLoading ..." @default.
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- W2068228017 title "Mifepristone Inhibits GRβ Coupled Prostate Cancer Cell Proliferation" @default.
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