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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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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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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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Journal Article
Inhibition of Enhancer of Zeste Homolog 2 (EZH2) Expression Is Associated With Decreased Tumor Cell Proliferation, Migration, and Invasion in Endometrial Cancer Cell Lines
2013
Overview
ObjectiveTo investigate the impact of enhancer of zeste homolog 2 (EZH2) expression on endometrial cancer cell line behavior.Materials and MethodsEnhancer of zeste homolog 2 expression levels were compared between the nonmalignant 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. Enhancer of zeste homolog 2 expression in endometrial cancer tissue specimens was examined using immunohistochemistry. Comparison of differences between control and short-hairpin EZH2 cell lines was performed using the Student t test and the Fischer exact test.ResultsEnhancer of zeste homolog 2 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 the G2/M phase. 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. Enhancer of zeste homolog 2 expression in human tissue samples was significantly associated with increased stage, grade, depth of invasion, and nodal metastasis.ConclusionsEnhancer of zeste homolog 2 expression is associated with tumor cell proliferation, migration, and invasion in 3 endometrial cancer cell lines as well as with increased stage, grade, depth of invasion, and nodal metastasis in human cancer tissue specimens. Further investigation into this potential therapeutic target is warranted.
Publisher
Elsevier Inc,Copyright by IGCS and ESGO,Elsevier Limited
Subject
/ Aged
/ Endometrial Neoplasms - genetics
/ Endometrial Neoplasms - metabolism
/ Endometrial Neoplasms - pathology
/ Enhancer of Zeste Homolog 2 Protein
/ EZH2
/ Female
/ Humans
/ Invasion
/ Neoplasm Recurrence, Local - genetics
/ Neoplasm Recurrence, Local - metabolism
/ Neoplasm Recurrence, Local - pathology
/ Polycomb Repressive Complex 2 - antagonists & inhibitors
/ Polycomb Repressive Complex 2 - genetics
/ Polycomb Repressive Complex 2 - metabolism
/ Real-Time Polymerase Chain Reaction
/ Reverse Transcriptase Polymerase Chain Reaction
