CtBP2 modulates the androgen receptor to promote prostate cancer progression

Ken Ichi Takayama, Takashi Suzuki, Tetsuya Fujimura, Tomohiko Urano, Satoru Takahashi, Yukio Homma, Satoshi Inoue

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

The androgen receptor (AR) is the key driver of both early and advanced prostate cancer, making a complete understanding of its regulation important. Here, we report the identification of multiple AR-binding sites in the gene encoding the transcription factor CtBP2 (carboxyl terminal-binding protein), genetic variations of which have been associated with prostate cancer susceptibility. Notably, we found that SNPs in the human CTBP2 gene that were associated with prostate cancer development were correlated with AR-enhancer activity. High CtBP2 expression levels correlated with poor prognosis in patients, whereas CtBP2 silencing reduced tumor growth in a mouse xenograft model of human prostate cancer. Consistent with its function as a transcriptional corepressor, CtBP2 repressed tumor-suppressor genes and AR corepressors in prostate cancer cells, such as NCOR and RIP140, by binding with AR to the promoter enhancers of these genes. Global gene-expression analyses revealed a positive effect on androgen-mediated gene expression, and CtBP2 silencing was found to increase AR interactions with corepressors that limit histone modification. Overall, our results show how CtBP2 contributes to prostate cancer progression by modulating AR and oncogenic signaling.

Original languageEnglish
Pages (from-to)6542-6553
Number of pages12
JournalCancer Research
Volume74
Issue number22
DOIs
Publication statusPublished - 2014 Nov 15

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Takayama, K. I., Suzuki, T., Fujimura, T., Urano, T., Takahashi, S., Homma, Y., & Inoue, S. (2014). CtBP2 modulates the androgen receptor to promote prostate cancer progression. Cancer Research, 74(22), 6542-6553. https://doi.org/10.1158/0008-5472.CAN-14-1030