title: Amyloid precursor protein is a primary androgen target gene that promotes prostate cancer growth.
abstract: Androgen receptor (AR) is a critical transcription factor that regulates various target genes and contributes to the pathophysiology of prostate cancer hormone dependently. Here, we identify amyloid precursor protein (APP) as a primary androgen target through chromatin immunoprecipitation (ChIP) combined with genome tiling array analysis (ChIP-chip). ChIP-treated DNA were obtained from prostate cancer LNCaP cells with R1881 or vehicle treatment using AR or acetylated histone H3 antibodies. Ligand-dependent AR binding was further enriched by PCR subtraction. Using chromosome 21/22 arrays, we identified APP as one of the androgen-regulated genes with adjacent functional AR binding sites. APP expression is androgen-inducible in LNCaP cells and APP immunoreactivity was correlated with poor prognosis in patients with prostate cancer. Gain-of-function and loss-of-function studies revealed that APP promotes the tumor growth of prostate cancer. The present study reveals a novel APP-mediated pathway responsible for the androgen-dependent growth of prostate cancer. Our findings will indicate that APP could be a potential molecular target for the diagnosis and treatment of prostate cancer.
authors.affiliation: Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Takayama
authors.forename: Shuichi
authors.initials: S
authors.lastname: Tsutsumi
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Kuniko
authors.initials: K
authors.lastname: Horie-Inoue
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ikeda
authors.forename: Kiyofumi
authors.initials: K
authors.lastname: Kaneshiro
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Fujimura
authors.forename: Jinpei
authors.initials: J
authors.lastname: Kumagai
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Urano
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Sakaki
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Shirahige
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
authors.forename: Tadaichi
authors.initials: T
authors.lastname: Kitamura
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Ouchi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Aburatani
authors.forename: Satoshi
authors.initials: S
authors.lastname: Inoue
mesh_terms: D000107:Acetylation; D000368:Aged; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis / Q000235:genetics*; D000728:Androgens / Q000502:physiology; D000818:Animals; D001665:Binding Sites; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D048708:Cell Growth Processes / Q000502:physiology; D047369:Chromatin Immunoprecipitation; D015972:Gene Expression Regulation, Neoplastic; D006657:Histones / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D058255:Protease Nexins; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics*
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D000728:Androgens; D014408:Biomarkers, Tumor; D006657:Histones; D058255:Protease Nexins; D012333:RNA, Messenger; D011944:Receptors, Androgen; D011956:Receptors, Cell Surface