Amyloid precursor protein is a primary androgen target gene that promotes prostate cancer growth

Ken Ichi Takayama, Shuichi Tsutsumi, Takashi Suzuki, Kuniko Horie-Inoue, Kazuhiro Ikeda, Kiyofumi Kaneshiro, Tetsuya Fujimura, Jinpei Kumagai, Tomohiko Urano, Yoshiyuki Sakaki, Katsuhiko Shirahige, Hironobu Sasano, Satoru Takahashi, Tadaichi Kitamura, Yasuyoshi Ouchi, Hiroyuki Aburatani, Satoshi Inoue

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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.

Original languageEnglish
Pages (from-to)137-142
Number of pages6
JournalCancer Research
Volume69
Issue number1
DOIs
Publication statusPublished - 2009 Jan 1

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Takayama, K. I., Tsutsumi, S., Suzuki, T., Horie-Inoue, K., Ikeda, K., Kaneshiro, K., Fujimura, T., Kumagai, J., Urano, T., Sakaki, Y., Shirahige, K., Sasano, H., Takahashi, S., Kitamura, T., Ouchi, Y., Aburatani, H., & Inoue, S. (2009). Amyloid precursor protein is a primary androgen target gene that promotes prostate cancer growth. Cancer Research, 69(1), 137-142. https://doi.org/10.1158/0008-5472.CAN-08-3633