Human heterochromatin protein 1 isoform HP1 beta enhances androgen receptor activity and is implicated in prostate cancer growth

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 1 beta (HP1 beta), but not HP1 alpha or HP1 gamma was found to be an AR cofactor. HP1 beta 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, HP1 beta expressions correlated with Gleason score and tri-methylation levels of histone H3 lysine 9. Silencing of HP1 beta 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, HP1 beta was overexpressed in castration-resistant LNCaP derivative CxR cells, and HP1 beta knockdown also suppressed the cell growth in CxR cells. These findings indicate that HP1 beta is involved in the proliferation of AR-expressing PCa cells and progression to CRPC as an AR coactivator. Modulation of HP1 beta expression or function might be a useful strategy for developing novel therapeutics for PCa, even in CRPC. Endocrine-Related Cancer (2010) 17 455-467