TY - JOUR
T1 - Amyloid precursor protein is a primary androgen target gene that promotes prostate cancer growth
AU - Takayama, Ken Ichi
AU - Tsutsumi, Shuichi
AU - Suzuki, Takashi
AU - Horie-Inoue, Kuniko
AU - Ikeda, Kazuhiro
AU - Kaneshiro, Kiyofumi
AU - Fujimura, Tetsuya
AU - Kumagai, Jinpei
AU - Urano, Tomohiko
AU - Sakaki, Yoshiyuki
AU - Shirahige, Katsuhiko
AU - Sasano, Hironobu
AU - Takahashi, Satoru
AU - Kitamura, Tadaichi
AU - Ouchi, Yasuyoshi
AU - Aburatani, Hiroyuki
AU - Inoue, Satoshi
N1 - Copyright:
Copyright 2009 Elsevier B.V., All rights reserved.
PY - 2009/1/1
Y1 - 2009/1/1
N2 - 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.
AB - 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.
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U2 - 10.1158/0008-5472.CAN-08-3633
DO - 10.1158/0008-5472.CAN-08-3633
M3 - Article
C2 - 19117996
AN - SCOPUS:58249094850
VL - 69
SP - 137
EP - 142
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 1
ER -