Steroid hormonal regulation of growth, prostate specific antigen secretion, and transcription mediated by the mutated androgen receptor in CWR22Rv1 human prostate carcinoma cells

Molecular and Cellular Endocrinology
Barbara J AttardiJerry R Reel

Abstract

CWR22Rv1 (22Rv1) is an androgen-responsive human prostate carcinoma cell line derived from a primary prostate tumor that expresses mutant (H874Y) androgen receptors (AR) and secretes low levels of prostate specific antigen (PSA). In this study, we examined the effects of various androgens and other steroid hormones on proliferation of 22Rv1 cells, PSA secretion, and transactivation. Incubation of 22Rv1 cells with various concentrations of testosterone resulted in a dose-dependent 50-80% increase in growth over 72 h. PSA release and transactivation of PRE2-tk-LUC in 22Rv1 cells were stimulated by low concentrations of natural and synthetic androgens (EC(50)s = 10(-10) to 10(-9)M) and a broad range of other classes of steroid hormones, albeit with lower potency. Uniform positive immunocytochemical staining was observed in 22Rv1 cell nuclei with mouse monoclonal antibodies to human AR. Competitive binding assays indicated that the mutant AR in 22Rv1 cytosol is more promiscuous than a wild-type AR (ARLBD: rat AR ligand binding domain). Testosterone (10(-8)M)-induced PSA release and transactivation were blocked by both antiandrogens and antiprogestins with IC(50)s of 10(-7) to 10(-6)M. At high concentration (10(-6)M), these antagoni...Continue Reading

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Citations

Jan 5, 2014·Cancer Metastasis Reviews·Zoran Culig, Frédéric R Santer
Jul 30, 2008·Proceedings of the National Academy of Sciences of the United States of America·Patrick S MitchellMuneesh Tewari
Mar 1, 2013·Endocrine-related Cancer·Natalie SampsonIris E Eder
Sep 13, 2011·Biochemical Pharmacology·Thomas AndrieuBrigitte M Frey
Nov 28, 2009·The Journal of Steroid Biochemistry and Molecular Biology·Barbara J AttardiAlvin M Matsumoto
Apr 9, 2013·International Journal of Cancer. Journal International Du Cancer·Naokazu IbukiMichael E Cox
Nov 5, 2011·International Journal of Cancer. Journal International Du Cancer·Ching-Yuan WuHong-Yo Kang
Apr 20, 2006·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Hyun-Jung KimMi-Sook Dong
Jan 17, 2012·Molecular and Cellular Endocrinology·Sathish Kasina, Jill A Macoska
Jul 9, 2013·Biochimica Et Biophysica Acta·Paolo PaoliPaola Chiarugi
Dec 18, 2016·International Urology and Nephrology·Jieping Hu, Qingke Chen
Jan 15, 2009·The Journal of Clinical Endocrinology and Metabolism·Tomoko KitagawaMitsuhiro Kawata
Aug 20, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Chin-Hsien TsaiPei-Wen Hsiao
May 28, 2021·EMBO Molecular Medicine·Marie ShamseddinCathrin Brisken

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