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: Takashi Kobayashi, Eijiro Nakamura, Yosuke Shimizu, Naoki Terada, Atsushi Maeno, Go Kobori, Tomomi Kamba, Toshiyuki Kamoto, Osamu Ogawa, Takahiro Inoue
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 387 Issue 1 Pg. 196-201 (Sep 11 2009) ISSN: 1090-2104 [Electronic] United States
• PMID: 19577536 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CCND2 protein, human
• Cyclin D2
• Cyclins
• Receptors, Androgen

Topics

• Cell Line, Tumor
• Cell Proliferation
• Cell Transformation, Neoplastic (genetics)
• Cyclin D2
• Cyclins (genetics, metabolism)
• Gene Deletion
• Gene Expression Regulation, Neoplastic
• Gene Knockdown Techniques
• Humans
• Male
• Mutation
• Prostatic Neoplasms (genetics, pathology)
• Protein Structure, Tertiary
• Receptors, Androgen (metabolism)