Androgen receptor or estrogen receptor-β blockade alters DHEA-, DHT-, and E2-induced proliferation and PSA production in human prostate cancer cells
Androgen receptor or estrogen receptor-β blockade alters DHEA-, DHT-, and E2-induced proliferation and PSA production in human prostate cancer cells
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DOI：
10.1002/pros.20585
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发表时间：
2007-08-01
期刊：
影响因子：
2.8
通讯作者：
Blackman, Marc R.
中科院分区：
文献类型：
--
作者：
Arnold, Julia T.;Liu, Xunxian;Blackman, Marc R.
背景资料。脱氢表雄酮(DHEA)是一种内源性类固醇，在人体前列腺中代谢为雄激素和/或雌激素。脱氢表雄酮水平随着年龄的增长而下降，使用脱氢表雄酮补充剂来延缓衰老过程具有未经证实的有效性和安全性。用LNCaP和LAPC-4前列腺癌细胞来确定DHEA是否通过雄激素受体(AR)和/或ERβ来调节前列腺特异性抗原(PSA)的产生和增殖。方法：研究方法。用DHEA、DHT或E-2处理细胞，用AR(Casodex R Bialutamine)或ER(ICI 182,780)拮抗剂或siRNA对各自的受体进行处理。用四甲基偶氮唑盐比色法检测细胞增殖，实时荧光定量聚合酶链式反应和酶联免疫吸附试验检测PSA基因和蛋白的分泌。通过免疫共沉淀研究和荧光共聚焦显微镜分析AR和ERβ的相关性。结果。DHEA-、T-和E-2诱导的LNCaP细胞的增殖可被Casodex钝化，但不能被ICI处理。在LNCaP细胞中，Casodex和ICI抑制激素诱导的PSA的产生。在LAPC-4细胞中，DHT刺激的PSA mRNA可被Casodex和ICI抑制，而DHEA的最小刺激作用可被ICI所抑制。SiRNAs的使用证实了AR和ERβ参与了激素诱导的PSA的产生，而AR-ERβ的共同联系是通过免疫沉淀和核共定位来实现的。结论。这些发现支持AR和ERβ参与介导DHEA、DHT和E2诱导的前列腺癌细胞中PSA的表达。前列腺癌67：1152-1162,2007。(C)2007年Wiley-Liss，Inc.
BACKGROUND. Dehydroepiandrosterone (DHEA) is an endogenous steroid that is metabolized to androgens and/or estrogens in the human prostate. DHEA levels decline with age, and use of DHEA supplements to retard the aging process is of unproved effectiveness and safety. LNCaP and LAPC-4 prostate cancer cells were used to determine whether DHEA-modulated proliferation and prostate specific antigen (PSA) production were mediated via the androgen receptor (AR) and/or ER beta. METHODS. Cells were treated with DHEA, DHT, or E-2 and antagonists to AR (Casodex R bicalutamide) or ER (ICI 182,780) or siRNA to the respective receptors. Proliferation was assessed by MTT assay and PSA mRNA and protein secretion were measured by quantitative real-time PCR and ELISA. Associations of AR and ER beta were analyzed by co-immunoprecipitation studies and fluorescent confocal microscopy. RESULTS. DHEA-, T-, and E-2-induced proliferation of LNCaP cells was blunted by Casodex but not by ICI treatment. In LNCaP cells, Casodex and ICI suppressed hormone-induced PSA production. In LAPC-4 cells, DHT-stimulated PSA mRNA was inhibited by Casodex and ICI, and the minimal stimulation by DHEA was inhibited by ICI. Use of siRNAs confirmed involvement of AR and ER beta in hormone-induced PSA production while AR-ER beta co-association was suggested by immunoprecipitation and nuclear co-localization. CONCLUSIONS. These findings support involvement of both AR and ER beta in mediating DHEA-, DHT-, and E2-induced PSA expression in prostate cancer cells. Prostate 67:1152-1162, 2007. (c) 2007 Wiley-Liss, Inc.