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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
  1. Ramez N. Eskander, MD*,
  2. Tao Ji, MD,
  3. Be Huynh, MD,
  4. Rooba Wardeh, MD,
  5. Leslie M. Randall, MD* and
  6. Bang Hoang, MD
  1. *Division of Gynecologic Oncology, Department of Obstetrics and Gynecology,
  2. Division of Orthopedic Surgical Oncology, Department of Orthopedics, and
  3. Department of Pathology, University of California Irvine Medical Center, Irvine, CA.
  1. Address correspondence and reprint requests to Ramez N. Eskander, MD, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of California Irvine Medical Center, 101 The City Drive South, Bldg 56, Suite 260, Irvine, CA. E-mail: Eskander@uci.edu.

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 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.

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.

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

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Footnotes

  • This work was supported by award number P30CA062203 from the National Cancer Institute, and NIH training grant 2T32CA060396-16A1.

  • The authors declare no conflicts of interest.

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