Transcriptional activity of c-Jun is critical for the suppression of AR function

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• 作者：Chih-Chao Hsu ; Chang-Deng Hu ; ^{hu1@purdue.edu}
• 关键词：AP-1 ; activator protein 1 ; CRPC ; castration-resistant prostate cancer ; DBD ; DNA-binding domain ; ARE ; androgen-response element ; DHT ; dihydrotestosterone ; bZIP ; basic region leucine zipper ; TRE ; TPA-responsive elements ; CRE ; cyclic AMP-responsive elements
• 刊名：Molecular and Cellular Endocrinology
• 出版年：2013
• 出版时间：15 June, 2013
• 年：2013
• 卷：372
• 期：1-2
• 页码：12-22
• 全文大小：1938 K

文摘

Androgen receptor (AR) signaling plays a pivotal role in growth and survival of prostate cancer cells. c-Jun is an important member of the activator protein 1 (AP-1) family and was shown to interact with AR. However, the role of c-Jun in AR signaling remains controversial, with being a coactivator or a corepressor reported. Here, utilizing multiple approaches, we show that c-Jun efficiently inhibits AR activity and the growth of prostate cancer cells. Overexpression of c-Jun inhibits not only the activities of various androgen-responsive promoters but also the transcripts of multiple AR target genes. Interestingly, long-term c-Jun overexpression also down-regulates AR expression at both the protein and mRNA levels. Molecular analysis suggests that c-Jun inhibits AR transactivation potential via an unknown target gene. The inhibition of AR by c-Jun occurs in both hormone na?ve and castration-resistant prostate cancer cells. Our results unravel a novel mechanism by which c-Jun antagonizes the AR signaling.