RUNX1, an androgen- and EZH2-regulated gene, has differential roles in AR-dependent and -independent prostate cancer
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Ken-ichi Takayama1,2, Takashi Suzuki3, Shuichi Tsutsumi4, Tetsuya Fujimura5, Tomohiko Urano1,2, Satoru Takahashi6, Yukio Homma5, Hiroyuki Aburatani4 and Satoshi Inoue1,2,7
1 Department of Anti-Aging Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
2 Department of Geriatric Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
3 Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
4 Genome Science Division, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Meguro-ku, Tokyo, Japan
5 Department of Urology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
6 Department of Urology, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan
7 Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Hidaka, Saitama, Japan
Satoshi Inoue, email:
Keywords: RUNX1, androgen receptor, EZH2, prostate cancer
Received: October 02, 2014 Accepted: December 09, 2014 Published: December 10, 2014
Androgen receptor (AR) signaling is essential for the development of prostate cancer. Here, we report that runt-related transcription factor (RUNX1) could be a key molecule for the androgen-dependence of prostate cancer. We found RUNX1 is a target of AR and regulated positively by androgen. Our RUNX1 ChIP-seq analysis indicated that RUNX1 is recruited to AR binding sites by interacting with AR. In androgen-dependent cancer, loss of RUNX1 impairs AR-dependent transcription and cell growth. The RUNX1 promoter is bound by enhancer of zeste homolog 2 (EZH2) and is negatively regulated by histone H3 lysine 27 (K27) trimethylation. Repression of RUNX1 is important for the growth promotion ability of EZH2 in AR-independent cells. In clinical prostate cancer samples, the RUNX1 expression level is negatively associated with EZH2 and that RUNX1 loss correlated with poor prognosis. These results indicated the significance of RUNX1 for androgen-dependency and that loss of RUNX1 could be a key step for the progression of prostate cancer.
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