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多梳蛋白家族成员EZH2调节人前列腺癌细胞中的肌动蛋白聚合。

The Polycomb Group protein EZH2 regulates actin polymerization in human prostate cancer cells.

作者信息

Bryant R J, Winder S J, Cross S S, Hamdy F C, Cunliffe V T

机构信息

MRC Centre for Developmental and Biomedical Genetics, University of Sheffield, Sheffield, United Kingdom.

出版信息

Prostate. 2008 Feb 15;68(3):255-63. doi: 10.1002/pros.20705.

DOI:10.1002/pros.20705
PMID:18095286
Abstract

BACKGROUND

The Polycomb Group protein EZH2 is implicated in prostate cancer progression. EZH2 promotes prostate cancer cell proliferation and invasiveness. We describe a link between EZH2 function and actin polymerization in prostate cancer cells.

METHODS

Nuclear and cytoplasmic EZH2 expression in benign and malignant prostate tissue samples was assessed. An association between EZH2 function and actin polymerization in prostate cancer cells was investigated using siRNA-mediated knock-down of EZH2. Effects of EZH2 knock-down on actin polymerization dynamics were analyzed biochemically using immunoblot analysis of cell lysate fractions, and morphologically using immunocytochemistry.

RESULTS

Cytoplasmic EZH2 is expressed at low levels in benign prostate epithelial cells and over-expressed in prostate cancer cells. Cytoplasmic EZH2 expression levels correlate with nuclear EZH2 expression in prostate cancer samples. Knock-down of EZH2 in PC3 prostate cancer cells increases the amount of F-actin polymerization, cell size, and formation of actin-rich filaments.

CONCLUSIONS

Cytoplasmic EZH2 is over-expressed in prostate cancer cells. EZH2 function promotes a reduction in the pool of insoluble F-actin in invasive prostate cancer cells. EZH2 may regulate actin polymerization dynamics and thereby promote prostate cancer cell motility and invasiveness.

摘要

背景

多梳蛋白家族成员EZH2与前列腺癌进展有关。EZH2促进前列腺癌细胞增殖和侵袭。我们描述了前列腺癌细胞中EZH2功能与肌动蛋白聚合之间的联系。

方法

评估良性和恶性前列腺组织样本中核内和胞质EZH2的表达。使用小干扰RNA介导的EZH2敲低研究前列腺癌细胞中EZH2功能与肌动蛋白聚合之间的关联。通过对细胞裂解物组分进行免疫印迹分析,从生化角度分析EZH2敲低对肌动蛋白聚合动力学的影响,并通过免疫细胞化学从形态学角度进行分析。

结果

胞质EZH2在良性前列腺上皮细胞中低水平表达,在前列腺癌细胞中过表达。前列腺癌样本中胞质EZH2表达水平与核内EZH2表达相关。在PC3前列腺癌细胞中敲低EZH2会增加F-肌动蛋白聚合量、细胞大小以及富含肌动蛋白的细丝形成。

结论

胞质EZH2在前列腺癌细胞中过表达。EZH2功能促进侵袭性前列腺癌细胞中不溶性F-肌动蛋白池的减少。EZH2可能调节肌动蛋白聚合动力学,从而促进前列腺癌细胞的运动性和侵袭性。

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