title: Restoration of cyclin D2 has an inhibitory potential on the proliferation of LNCaP cells.
abstract: Despite well known oncogenic function of G1-S cell-cycle progression, cyclin D2 (CCND2) is often silenced epigenetically in prostate cancers. Here we show that CCND2 has an inhibitory potential on the proliferation of androgen receptor (AR)-dependent prostate cancer LNCaP cells. Forced expression of CCND2 suppressed the proliferative ability and induced cell death in LNCaP cells in a cdk-independent manner. Knocking down CCND2 restored the proliferation of LNCaP subclones with relatively high CCND2 expression and low proliferative profiles. Immunoprecipitation using deletion mutants of CCND2 indicated that a central domain of CCND2 is required for binding to AR. A deletion mutant lacking the central domain failed to hinder LNCaP cells. Collectively, our results indicated that CCND2 inhibits cell proliferation of AR-dependent prostate cancer through the interaction with AR. Our study suggests that restoration of CCND2 expression potentially prevents the carcinogenesis of prostate cancer, which is mostly AR-dependent in the initial settings.
authors: Department of Urology, Kyoto University, Graduate School of Medicine, 54 Shogoinkawahara-cho, Sakyo-ku, Kyoto, Japan.
authors: Takashi
authors: T
authors: Kobayashi
authors: Eijiro
authors: E
authors: Nakamura
authors: Yosuke
authors: Y
authors: Shimizu
authors: Naoki
authors: N
authors: Terada
authors: Atsushi
authors: A
authors: Maeno
authors: Go
authors: G
authors: Kobori
authors: Tomomi
authors: T
authors: Kamba
authors: Toshiyuki
authors: T
authors: Kamoto
authors: Osamu
authors: O
authors: Ogawa
authors: Takahiro
authors: T
authors: Inoue
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D056742:Cyclin D2; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D009154:Mutation; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*; D017434:Protein Structure, Tertiary; D011944:Receptors, Androgen / Q000378:metabolism*
chemical_list: C080336:CCND2 protein, human; D056742:Cyclin D2; D016213:Cyclins; D011944:Receptors, Androgen