title: RUNX1, an androgen- and EZH2-regulated gene, has differential roles in AR-dependent and -independent prostate cancer.
abstract: 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.
authors.affiliation: Department of Anti-Aging Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.|Department of Geriatric Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Takayama
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Genome Science Division, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Meguro-ku, Tokyo, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Tsutsumi
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Fujimura
authors.affiliation: Department of Anti-Aging Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.|Department of Geriatric Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Urano
authors.affiliation: Department of Urology, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Homma
authors.affiliation: Genome Science Division, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Meguro-ku, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Aburatani
authors.affiliation: Department of Anti-Aging Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.|Department of Geriatric Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.|Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Hidaka, Saitama, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Inoue
mesh_terms: D000368:Aged; D000728:Androgens / Q000494:pharmacology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000378:metabolism*; D013196:Dihydrotestosterone / Q000494:pharmacology; D000071221:Enhancer of Zeste Homolog 2 Protein; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D057809:HEK293 Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008745:Methylation; D008875:Middle Aged; D063151:Polycomb Repressive Complex 2 / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding; D034622:RNA Interference; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis
chemical_list: D000728:Androgens; D050676:Core Binding Factor Alpha 2 Subunit; D006657:Histones; C493728:RUNX1 protein, human; D011944:Receptors, Androgen; D013196:Dihydrotestosterone; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2