The polycomb group protein EZH2 regulates actin polymerization in human prostate cancer cells

被引:38
作者
Bryant, R. J. [1 ,2 ,3 ]
Winder, S. J. [2 ]
Cross, S. S. [4 ]
Hamdy, F. C. [1 ,3 ]
Cunliffel, V. T. [1 ,2 ]
机构
[1] Univ Sheffield, MRC Ctr Dev & Biomed Genet, Sheffield, S Yorkshire, England
[2] Univ Sheffield, Dept Biomed Sci, Sheffield, S Yorkshire, England
[3] Univ Sheffield, Sch Med & Biomed Sci, Acad Urol Unit, Sheffield, S Yorkshire, England
[4] Univ Sheffield, Sch Med & Biomed Sci, Acad Pathol Unit, Sheffield, S Yorkshire, England
基金
英国医学研究理事会; 英国惠康基金;
关键词
EZH2; prostate cancer; cytoskeleton; actin polymerization;
D O I
10.1002/pros.20705
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:255 / 263
页数:9
相关论文
共 22 条
[11]   Gene repression by Polycomb group protein complexes: a distinct complex for every occasion? [J].
Otte, AP ;
Kwaks, THJ .
CURRENT OPINION IN GENETICS & DEVELOPMENT, 2003, 13 (05) :448-454
[12]   Molecular functions of nuclear actin in transcription [J].
Percipalle, P ;
Visa, N .
JOURNAL OF CELL BIOLOGY, 2006, 172 (07) :967-971
[13]   Cellular motility driven by assembly and disassembly of actin filaments [J].
Pollard, TD ;
Borisy, GG .
CELL, 2003, 112 (04) :453-465
[14]   Mutant actins demonstrate a role for unpolymerized actin in control of transcription by serum response factor [J].
Posern, G ;
Sotiropoulos, A ;
Treisman, R .
MOLECULAR BIOLOGY OF THE CELL, 2002, 13 (12) :4167-4178
[15]   RELATED CHROMOSOME BINDING-SITES FOR ZESTE, SUPPRESSORS OF ZESTE AND POLYCOMB GROUP PROTEINS IN DROSOPHILA AND THEIR DEPENDENCE ON ENHANCER OF ZESTE FUNCTION [J].
RASTELLI, L ;
CHAN, CS ;
PIRROTTA, V .
EMBO JOURNAL, 1993, 12 (04) :1513-1522
[16]   Multiplex biomarker approach for determining risk of prostate-specific antigen-defined recurrence of prostate cancer [J].
Rhodes, DR ;
Sanda, MG ;
Otte, AP ;
Chinnaiyan, AM ;
Rubin, MA .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2003, 95 (09) :661-668
[17]   The gene for polycomb group protein enhancer of zeste homolog 2 (EZH2) is amplified in late-stage prostate cancer [J].
Saramaki, Outi R. ;
Tammela, Teuvo L. J. ;
Martikainen, Paula M. ;
Vessella, Robert L. ;
Visakorpi, Tapio .
GENES CHROMOSOMES & CANCER, 2006, 45 (07) :639-645
[18]   The comings and goings of actin: coupling protrusion and retraction in cell motility [J].
Small, JV ;
Resch, GP .
CURRENT OPINION IN CELL BIOLOGY, 2005, 17 (05) :517-523
[19]   Polycomb group protein Ezh2 controls actin polymerization and cell signaling [J].
Su, I ;
Dobenecker, MW ;
Dickinson, E ;
Oser, M ;
Basavaraj, A ;
Marqueron, R ;
Viale, A ;
Reinberg, D ;
Wülfing, C ;
Tarakhovsky, A .
CELL, 2005, 121 (03) :425-436
[20]   Efficient delivery of small interfering RNA to bone-metastatic tumors by using atelocollagen in vivo [J].
Takeshita, F ;
Minakuchi, Y ;
Nagahara, S ;
Honma, K ;
Sasaki, H ;
Hirai, K ;
Teratani, T ;
Namatame, N ;
Yamamoto, Y ;
Hanai, K ;
Kato, T ;
Sano, A ;
Ochiya, T .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (34) :12177-12182