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

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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. Prostate 68: 255–263, 2008.