Restoration of cyclin D2 has an inhibitory potential on the proliferation of LNCaP cells.
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.
Kobayashi
Takashi
T
Department of Urology, Kyoto University, Graduate School of Medicine, 54 Shogoinkawahara-cho, Sakyo-ku, Kyoto, Japan.
Nakamura
Eijiro
E
Shimizu
Yosuke
Y
Terada
Naoki
N
Maeno
Atsushi
A
Kobori
Go
G
Kamba
Tomomi
T
Kamoto
Toshiyuki
T
Ogawa
Osamu
O
Inoue
Takahiro
T
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*
C080336:CCND2 protein, human; D056742:Cyclin D2; D016213:Cyclins; D011944:Receptors, Androgen