文章基本信息

标题：Estrogen receptor–β activated apoptosis in benign hyperplasia and cancer of the prostate is androgen independent and TNFα mediated
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作者：Stephen J. McPherson ; Shirin Hussain ; Preetika Balanathan 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2010
卷号：107
期号：7
页码：3123-3128
DOI：10.1073/pnas.0905524107
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Prostate cancer (PCa) and benign prostatic hyperplasia (BPH) are androgen-dependent diseases commonly treated by inhibiting androgen action. However, androgen ablation or castration fail to target androgen-independent cells implicated in disease etiology and recurrence. Mechanistically different to castration, this study shows beneficial proapoptotic actions of estrogen receptor-{beta} (ER{beta}) in BPH and PCa. ER{beta} agonist induces apoptosis in prostatic stromal, luminal and castrate-resistant basal epithelial cells of estrogen-deficient aromatase knock-out mice. This occurs via extrinsic (caspase-8) pathways, without reducing serum hormones, and perturbs the regenerative capacity of the epithelium. TNF{alpha} knock-out mice fail to respond to ER{beta} agonist, demonstrating the requirement for TNF{alpha} signaling. In human tissues, ER{beta} agonist induces apoptosis in stroma and epithelium of xenografted BPH specimens, including in the CD133+ enriched putative stem/progenitor cells isolated from BPH-1 cells in vitro. In PCa, ER{beta} causes apoptosis in Gleason Grade 7 xenografted tissues and androgen-independent cells lines (PC3 and DU145) via caspase-8. These data provide evidence of the beneficial effects of ER{beta} agonist on epithelium and stroma of BPH, as well as androgen-independent tumor cells implicated in recurrent disease. Our data are indicative of the therapeutic potential of ER{beta} agonist for treatment of PCa and/or BPH with or without androgen withdrawal.
关键词：castration ; steroid receptors ; selective estrogen receptor modulators