Human heterochromatin protein 1 isoform HP1beta enhances androgen receptor activity and is implicated in prostate cancer growth.

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 1beta (HP1beta), but not HP1alpha or HP1gamma was found to be an AR cofactor. HP1beta 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, HP1beta expressions correlated with Gleason score and tri-methylation levels of histone H3 lysine 9. Silencing of HP1beta suppressed the growth of AR-expressing PCa cells by inducing cell-cycle arrest at the G(1) phase, similar to inhibition of androgen/AR signaling. Furthermore, HP1beta was overexpressed in castration-resistant LNCaP derivative CxR cells, and HP1beta knockdown also suppressed the cell growth in CxR cells. These findings indicate that HP1beta is involved in the proliferation of AR-expressing PCa cells and progression to CRPC as an AR coactivator. Modulation of HP1beta expression or function might be a useful strategy for developing novel therapeutics for PCa, even in CRPC.

journal_name

Endocr Relat Cancer

journal_title

Endocrine-related cancer

authors

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

doi

10.1677/ERC-09-0321

subject

Has Abstract

pub_date

2010-05-18 00:00:00

pages

455-67

issue

2

eissn

1351-0088

issn

1479-6821

pii

ERC-09-0321

journal_volume

17

pub_type

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