Peroxisome proliferator-activated receptor γ coactivator-1α interacts with the androgen receptor (AR) and promotes prostate cancer cell growth by activating the AR

Masaki Shiota, Akira Yokomizo, Yasuhiro Tada, Junichi Inokuchi, Katsunori Tatsugami, Kentaro Kuroiwa, Takeshi Uchiumi, Naohiro Fujimoto, Narihito Seki, Seiji Naito

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

There are currently few successful therapies for castration-resistant prostate cancer (CRPC). CRPC is thought to result from augmented activation of the androgen/androgen receptor (AR) signaling pathway, which could be enhanced by AR cofactors. In this study, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) was found to be an AR cofactor. PGC-1α interacted with the N-terminal domain of AR, was involved in the N- and C-terminal interaction of AR, and enhanced the DNA-binding ability of AR to androgen-responsive elements in the prostate-specific antigen enhancer and promoter regions to increase the transcription of AR target genes. Silencing of PGC-1α suppressed cell growth of AR-expressing prostate cancer (PCa) cells by inducing cell-cycle arrest at the G1 phase, similar to inhibition of androgen/AR signaling. Furthermore, PGC-1α knock-down also suppressed cell growth in the castration-resistant LNCaP-derivatives. These findings indicate that PGC-1α is involved in the proliferation of AR-expressing PCa cells by acting as an AR coactivator. Modulation of PGC-1α expression or function may offer a useful strategy for developing novel therapeutics for PCa, including CRPC, which depends on AR signaling by over-expressing AR and its coactivators.

Original languageEnglish
Pages (from-to)114-127
Number of pages14
JournalMolecular Endocrinology
Volume24
Issue number1
DOIs
Publication statusPublished - Jan 2010

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Endocrinology

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