Human heterochromatin protein 1 isoform HP1β enhances androgen receptor activity and is implicated in prostate cancer growth

M. Shiota, Y. Song, A. Yokomizo, Y. Tada, K. Kuroiwa, M. Eto, Y. Oda, J. Inokuchi, T. Uchiumi, N. Fujimoto, N. Seki, S. Naito

Research output: Contribution to journalArticle

16 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, heterochromatin protein 1β (HP1β), but not HP1α or HP1γ was found to be an AR cofactor. HP1β interacted with the AR, and enhanced the DNA-binding ability of AR to androgen-responsive element in the prostate-specific antigen enhancer and promoter regions, and to increase the transcription of AR target genes. In prostate cancer (PCa) tissues, HP1β expressions correlated with Gleason score and tri-methylation levels of histone H3 lysine 9. Silencing of HP1β suppressed the growth of AR-expressing PCa cells by inducing cell-cycle arrest at the G1 phase, similar to inhibition of androgen/AR signaling. Furthermore, HP1β was overexpressed in castration-resistant LNCaP derivative CxR cells, and HP1β knockdown also suppressed the cell growth in CxR cells. These findings indicate that HP1β is involved in the proliferation of AR-expressing PCa cells and progression to CRPC as an AR coactivator. Modulation of HP1β expression or function might be a useful strategy for developing novel therapeutics for PCa, even in CRPC.

Original languageEnglish
Pages (from-to)455-467
Number of pages13
JournalEndocrine-Related Cancer
Volume17
Issue number2
DOIs
Publication statusPublished - Jun 1 2010

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Oncology
  • Endocrinology
  • Cancer Research

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