Orphan nuclear receptor estrogen-related receptor-beta suppresses in vitro and in vivo growth of prostate cancer cells via p21(WAF1/CIP1) induction and as a potential therapeutic target in prostate cancer
Publication in refereed journal

香港中文大學研究人員

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摘要Recent studies indicate that estrogen-related receptors (ERRs) are involved in similar estrogen receptor (ER) regulatory pathways and play roles in energy and lipid metabolism. Here, we analysed the functional role of ERR beta in prostate cancer cell growth regulation in an androgen-sensitive and androgen-insensitive prostate cancer cell lines. ERR beta was expressed in normal human prostates, but exhibited a reduced expression in prostate cancer lesions. Stable ERR beta expression suppressed significantly cell proliferation and tumorigenicity of LNCaP and DU145 cells, accompanied by an S-phase suppression and increased p21 expression. Reporter and chromatin immunoprecipitation assays showed that ERRb could directly transactivate p21 gene promoter, which could be further enhanced by peroxisome proliferator-activated receptor-gamma coactivator-1 alpha. Truncation analysis showed that ERR beta-mediated p21 transactivation and prostate cancer cell growth inhibition required intact DNA-binding domain and AF2 domains in ERR beta. Interestingly, ERR beta displayed a cell cycle associated downregulated expression pattern in ERR beta-transduced and non-transduced cells. Finally, we showed that ERR beta-mediated growth inhibition could be potentiated by an ERRb/gamma agonist DY131. Knockdown of ERR beta by RNA interference could reduce the DY131-induced growth inhibition in prostate cancer cells. Taken together, our findings indicate that ERR beta performs a tumor suppressing function in prostate cancer cells, and targeting ERR beta could be a potential therapeutic strategy for prostate cancer.
著者Yu S, Wong YC, Wang XH, Ling MT, Ng CF, Chen S, Chan FL
期刊名稱Oncogene
出版年份2008
月份5
日期1
卷號27
期次23
出版社NATURE PUBLISHING GROUP
頁次3313 - 3328
國際標準期刊號0950-9232
電子國際標準期刊號1476-5594
語言英式英語
關鍵詞ERR beta; estrogen receptor-related; estrogen-related receptor; orphan nuclear receptor; prostate cancer; receptor; tumor suppression
Web of Science 學科類別Biochemistry & Molecular Biology; BIOCHEMISTRY & MOLECULAR BIOLOGY; Cell Biology; CELL BIOLOGY; Genetics & Heredity; GENETICS & HEREDITY; Oncology; ONCOLOGY

上次更新時間 2020-07-07 於 01:54