Bryant R J, Cross N A, Eaton C L, Hamdy F C, Cunliffe V T
MRC Centre Development for Developmental and Biomedical Genetics, University of Sheffield, Firth Court, Western Bank, Sheffield, United Kingdom.
Prostate. 2007 Apr 1;67(5):547-56. doi: 10.1002/pros.20550.
The transcriptional repressor EZH2 is implicated in control of cell proliferation in embryonic, immortalized and transformed cells. EZH2 expression in prostate cancer correlates with progression to hormone-refractory and metastatic disease, but it is unknown whether EZH2 plays a specific role in the acquisition of an advanced prostate cancer phenotype.
Using siRNA knockdown, we investigated the role of EZH2 in maintenance of prostate cancer cell proliferation and invasiveness. Using LNCaP cells with inducible EZH2 overexpression, we investigated whether EZH2 upregulation promotes an aggressive phenotype.
Knockdown of endogenous EZH2 reduced proliferation of androgen-responsive and androgen-independent prostate cancer cells. EZH2 knockdown also inhibited prostate cancer cell invasion. However, overexpression of EZH2 in androgen-responsive cancer cells did not appreciably affect either proliferation or invasiveness.
EZH2 promotes proliferation and invasion of prostate cancer cells, which can account for the correlation between EZH2 expression levels and an adverse prostate cancer prognosis.
转录抑制因子EZH2参与胚胎细胞、永生化细胞及转化细胞增殖的调控。前列腺癌中EZH2的表达与激素难治性和转移性疾病的进展相关，但EZH2在晚期前列腺癌表型的形成中是否发挥特定作用尚不清楚。
利用小干扰RNA敲低技术，我们研究了EZH2在维持前列腺癌细胞增殖和侵袭能力中的作用。利用可诱导EZH2过表达的LNCaP细胞，我们研究了EZH2上调是否促进侵袭性表型的形成。
敲低内源性EZH2可降低雄激素反应性和雄激素非依赖性前列腺癌细胞的增殖。EZH2敲低还抑制前列腺癌细胞的侵袭。然而，雄激素反应性癌细胞中EZH2的过表达对增殖或侵袭均无明显影响。
EZH2促进前列腺癌细胞的增殖和侵袭，这可以解释EZH2表达水平与前列腺癌不良预后之间的相关性。
