Inhibition of enhancer of zeste homolog 2 (ezh2) expression is associated with decreased tumor cell proliferation, migration, and invasion in endometrial cancer cell lines

Ramez N. Eskander, Tao Ji, Be Huynh, Rooba Wardeh, Leslie M. Randall, Bang Hoang

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Objective: To investigate the impact of enhancer of zeste homolog 2 (EZH2) expression on endometrial cancer cell line behavior. Materials and Methods: Enhancer 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. Results: Enhancer 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 expressionwas associatedwith an increase in the expression ofWnt pathway inhibitors sFRP1 and DKK3 and a concomitant decrease in A-catenin. Enhancer of zeste homolog 2 expression in human tissue samples was significantly associated with increased stage, grade, depth of invasion, and nodal metastasis. Conclusions: Enhancer 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.

Original languageEnglish (US)
Pages (from-to)997-1005
Number of pages9
JournalInternational Journal of Gynecological Cancer
Volume23
Issue number6
DOIs
StatePublished - Jul 2013
Externally publishedYes

Keywords

  • EZH2
  • Endometrial cancer
  • Invasion
  • Migration
  • Pathology
  • Uterine cancer

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

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