Peroxiredoxin 2 in the nucleus and cytoplasm distinctly regulates androgen receptor activity in prostate cancer cells

Masaki Shiota, Akira Yokomizo, Eiji Kashiwagi, Ario Takeuchi, Naohiro Fujimoto, Takeshi Uchiumi, Seiji Naito

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Currently, few therapies are effective against castration-resistant prostate cancer. Increased activation of the androgen/androgen receptor (AR) signaling pathway is thought to promote castration-resistant prostate cancer. Herein, we report that peroxiredoxin (Prx) gene expression in castration-resistant prostate cancer and hydrogen peroxide-resistant cells was upregulated. Prx2 was overexpressed in castration-resistant prostate cancer at the mRNA and protein levels and was localized to the nucleus and cytoplasm. Overexpression of Prx2 increased AR transactivation, whereas Prx2 overexpression in the nucleus suppressed AR transactivation. These effects of Prx2 on AR activity were abolished by the introduction of function-disrupting mutations into Cys 51 and Cys 172. Silencing Prx2 reduced the expression of androgen-regulated genes and suppressed the growth of AR-expressing prostate cancer cells by inducing cell-cycle arrest at the G1 phase. Furthermore, Prx2 knockdown also suppressed cell growth in castration-resistant prostate cancer cells. These findings indicate that Prx2 is involved in the proliferation of AR-expressing prostate cancer cells by modulating AR activity. Designing therapeutics targeting Prx2 may offer a novel strategy for developing treatments for prostate cancer, including castration-resistant prostate cancer, which is dependent on AR signaling.

Original languageEnglish
Pages (from-to)78-87
Number of pages10
JournalFree Radical Biology and Medicine
Volume51
Issue number1
DOIs
Publication statusPublished - Jul 1 2011

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology (medical)

Cite this