Human heterochromatin protein 1 isoforms regulate androgen receptor signaling in prostate cancer

Androgen receptor (AR) signaling is critical for the tumorigenesis and development of prostate cancer, as well as the progression to castration-resistant prostate cancer. We previously showed that the heterochromatin protein 1 (HP1) beta isoform plays a critical role in transactivation of AR signaling as an AR coactivator that promotes prostate cancer cell proliferation. However, the roles of other HP1 isoforms, HP1 alpha and HP1 gamma, in AR expression and prostate cancer remain unclear. Here, we found that knockdown of HP1 gamma, but not HP1 alpha, reduced AR expression and cell proliferation by inducing cell cycle arrest at G1 phase in LNCaP cells. Conversely, overexpression of full-length HP1 alpha and its C-terminal deletion mutant increased AR expression and cell growth, whereas overexpression of HP1 gamma had no effect. Similarly, HP1 alpha overexpression promoted 22Rv1 cell growth, whereas HP1 gamma knockdown reduced the proliferation of CxR cells, a castration-resistant LNCaP derivative. Taken together, HP1 isoforms distinctly augment AR signaling and cell growth in prostate cancer. Therefore, silencing of HP1 beta and HP1 gamma may be a promising therapeutic strategy for treatment of prostate cancer.