Inhibition of enhancer of zeste homolog 2 (EZH2) expression is associated with decreased tumor cell proliferation, migration, and invasion in endometrial cancer cell lines.
Inhibition of enhancer of zeste homolog 2 (EZH2) expression is associated with decreased tumor cell proliferation, migration, and invasion in endometrial cancer cell lines.
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DOI：
10.1097/igc.0b013e318296a265
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发表时间：
2013-07
期刊：
影响因子：
--
通讯作者：
Hoang B
中科院分区：
文献类型：
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作者：
Eskander RN;Ji T;Huynh B;Wardeh R;Randall LM;Hoang B
探讨增强子Zeste同源物2（EZH 2）表达对子宫内膜癌细胞系行为的影响。比较非恶性子宫内膜细胞系T-HESC与3种子宫内膜癌细胞系ECC-1、RL 95 -2和HEC 1-A之间EZH 2表达水平。建立了稳定的EZH 2敲低细胞系，并测定了对细胞增殖、迁移和侵袭的影响。荧光激活细胞分选用于检查EZH 2沉默对细胞周期进程的影响。采用免疫组化方法检测EZH 2在子宫内膜癌组织中的表达。使用student t检验和Fischer精确检验比较对照和shEZH 2细胞系之间的差异。相对于对照，EZH 2蛋白表达在所有3种癌细胞系和人子宫内膜癌组织标本中增加。RNA干扰EZH 2在ECC-1、RL 95 -2和HEC 1-A中的表达显著降低细胞增殖、迁移和侵袭。EZH 2表达下调导致停滞在G2/M期的细胞比例显著增加。EZH 2表达的RNA干扰与Wnt通路抑制剂sFRP 1和DKK 3表达的增加以及β-连环蛋白的伴随减少相关。EZH 2在人类组织样本中的表达与增加的分期、分级、浸润深度和淋巴结转移显著相关。EZH 2表达与3种子宫内膜癌细胞系中肿瘤细胞增殖、迁移和侵袭相关，以及与人类癌组织标本中分期、分级、浸润深度和淋巴结转移增加相关。有必要对这个潜在的治疗靶点进行进一步研究。
To investigate the impact of Enhancer of Zeste Homolog 2 (EZH2) expression on endometrial cancer cell line behavior. EZH2 expression levels were compared between the non-malignant endometrial cell line T-HESC, and 3 endometrial cancer cell lines, ECC-1, RL95-2 and HEC1-A. Stable EZH2 knockdown cell lines were created and the impact on cellular proliferation, migration and invasion were determined. Fluorescent activated cell sorting was used to examine effects of EZH2 silencing on cell cycle progression. EZH2 expression in endometrial cancer tissue specimens was examined using immunohistochemistry. Comparison of differences between control and shEZH2 cell lines was performed using student's t test and Fischer's exact test. EZH2 protein expression was increased in all 3 cancer cell lines, and human endometrial cancer tissue specimens relative to control. RNA interference of EZH2 expression in ECC-1, RL95-2, and HEC1-A significantly decreased cell proliferation, migration and invasion. Down regulation of EZH2 expression resulted in a significant increase in the proportion of cells arrested in G2/M. RNA interference of EZH2 expression was associated with an increase in the expression of Wnt pathway inhibitors sFRP1 and DKK3, and a concomitant decrease in β-catenin. EZH2 expression in human tissue samples was significantly associated with increased stage, grade, depth of invasion and nodal metastasis. EZH2 expression is associated with tumor cell proliferation, migration and invasion in 3 endometrial cancer cell lines, as well as increased stage, grade, depth of invasion and nodal metastasis in human cancer tissue specimens. Further investigation into this potential therapeutic target is warranted.