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

Momoe Itsumi, Masaki Shiota, Akira Yokomizo, Eiji Kashiwagi, Ario Takeuchi, Katsunori Tatsugami, Junichi Inokuchi, Yoohyun Song, Takeshi Uchiumi, Seiji Naito

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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) b 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, HP1a and HP1g, in AR expression and prostate cancer remain unclear. Here, we found that knockdown of HP1g, but not HP1a, reduced AR expression and cell proliferation by inducing cell cycle arrest at G1 phase in LNCaP cells. Conversely, overexpression of full-length HP1a and its C-terminal deletion mutant increased AR expression and cell growth, whereas overexpression of HP1g had no effect. Similarly, HP1a overexpression promoted 22Rv1 cell growth, whereas HP1g 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 HP1b and HP1g may be a promising therapeutic strategy for treatment of prostate cancer.

Original languageEnglish
Pages (from-to)401-409
Number of pages9
JournalJournal of Molecular Endocrinology
Volume50
Issue number3
DOIs
Publication statusPublished - Mar 27 2013

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Androgen Receptors
Prostatic Neoplasms
Protein Isoforms
Castration
Cell Proliferation
Growth
G1 Phase
Cell Cycle Checkpoints
heterochromatin-specific nonhistone chromosomal protein HP-1
Transcriptional Activation
Carcinogenesis

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Endocrinology

Cite this

Human heterochromatin protein 1 Isoforms regulate androgen receptor signaling in prostate cancer. / Itsumi, Momoe; Shiota, Masaki; Yokomizo, Akira; Kashiwagi, Eiji; Takeuchi, Ario; Tatsugami, Katsunori; Inokuchi, Junichi; Song, Yoohyun; Uchiumi, Takeshi; Naito, Seiji.

In: Journal of Molecular Endocrinology, Vol. 50, No. 3, 27.03.2013, p. 401-409.

Research output: Contribution to journalArticle

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