title: Human heterochromatin protein 1 isoforms regulate androgen receptor signaling in prostate cancer.
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) β 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, HP1α and HP1γ, in AR expression and prostate cancer remain unclear. Here, we found that knockdown of HP1γ, but not HP1α, reduced AR expression and cell proliferation by inducing cell cycle arrest at G1 phase in LNCaP cells. Conversely, overexpression of full-length HP1α and its C-terminal deletion mutant increased AR expression and cell growth, whereas overexpression of HP1γ had no effect. Similarly, HP1α overexpression promoted 22Rv1 cell growth, whereas HP1γ 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 HP1β and HP1γ may be a promising therapeutic strategy for treatment of prostate cancer.
authors.affiliation: Departments of Urology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Momoe
authors.initials: M
authors.lastname: Itsumi
authors.forename: Masaki
authors.initials: M
authors.lastname: Shiota
authors.forename: Akira
authors.initials: A
authors.lastname: Yokomizo
authors.forename: Eiji
authors.initials: E
authors.lastname: Kashiwagi
authors.forename: Ario
authors.initials: A
authors.lastname: Takeuchi
authors.forename: Katsunori
authors.initials: K
authors.lastname: Tatsugami
authors.forename: Junichi
authors.initials: J
authors.lastname: Inokuchi
authors.forename: Yoohyun
authors.initials: Y
authors.lastname: Song
authors.forename: Takeshi
authors.initials: T
authors.lastname: Uchiumi
authors.forename: Seiji
authors.initials: S
authors.lastname: Naito
mesh_terms: D045744:Cell Line, Tumor; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*
chemical_list: C000715593:CBX1 protein, human; C000715594:CBX5 protein, human; D002868:Chromosomal Proteins, Non-Histone; D020033:Protein Isoforms; D034741:RNA, Small Interfering; D011944:Receptors, Androgen; D000090266:Chromobox Protein Homolog 5