Enhancer of Zeste Homolog 2 Promotes the Proliferation and Invasion of Epithelial Ovarian Cancer Cells

Abstract

Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of the polycomb repressive complex 2 (PRC2) that includes noncatalytic subunits suppressor of zeste 12 (SUZ12) and embryonic ectoderm development (EED). When present in PRC2, EZH2 catalyzes trimethylation on lysine 27 residue of histone H3 (H3K27Me3), resulting in epigenetic silencing of gene expression. Here, we investigated the expression and function of EZH2 in epithelial ovarian cancer (EOC). When compared with primary human ovarian surface epithelial (pHOSE) cells, EZH2, SUZ12, and EED were expressed at higher levels in all 8 human EOC cell lines tested. Consistently, H3K27Me3 was also overexpressed in human EOC cell lines compared with pHOSE cells. EZH2 was significantly overexpressed in primary human EOCs (n ¼ 134) when compared with normal ovarian surface epithelium (n ¼ 46; P < 0.001). EZH2 expression positively correlated with expression of Ki67 (P < 0.001; a marker of cell proliferation) and tumor grade (P ¼ 0.034) but not tumor stage (P ¼ 0.908) in EOC. There was no correlation of EZH2 expression with overall (P ¼ 0.3) or disease-free survival (P ¼ 0.2) in high-grade serous histotype EOC patients (n ¼ 98). Knockdown of EZH2 expression reduced the level of H3K27Me3 and suppressed the growth of human EOC cells both in vitro and in vivo in xenograft models. EZH2 knockdown induced apoptosis of human EOC cells. Finally, we showed that EZH2 knockdown suppressed the invasion of human EOC cells. Together, these data demonstrate that EZH2 is frequently overexpressed in human EOC cells and its overexpression promotes the proliferation and invasion of human EOC cells, suggesting that EZH2 is a potential target for developing EOC therapeutics. Mol Cancer Res; 8(12); 1610-8. Ó2010 AACR.

Downregulation of Ezh2 expression by RNA interference induces cell cycle arrest in the G0/G1 phase and apoptosis in U87 human glioma cells

“…These data suggest that the Ezh2 gene plays a role in promoting the proliferation of glioma cells. Consistent with our findings, previous studies have also shown that the Ezh2 gene promotes the proliferation of lung (18), breast (9), thyroid (19), colon (20), ovarian (21), and pancreatic cancer cells (22). Therefore, we concluded that the Ezh2 gene plays an important role in the regulation of the proliferation of glioma cells.…”

Histone Methyltransferase hSETD1A Is a Novel Regulator of Metastasis in Breast Cancer

“…Furthermore, using an in vivo model, we observed significantly reduced metastatic potential in MDA-MB-231 cells following hSETD1A knockdown (Fig. 4).These findings are in clear agreement with other studies demonstrating that additional critical epigenetic modifiers, such as Ezh2, LSD1, JARID1, SUZ12, SET8, and various HDACs exhibit prominent effects on cancer cell proliferation, invasion, migration, angiogenesis, or metastatic activity (37,38,(59)(60)(61)(62)(63). In sum, current evidence firmly supports the conclusion that H3K4me3 and other epigenetic modifications exert a critical impact on cancer cell phenotype and behavior.…”

Up‐regulation of enhancer of zeste homolog 2 is associated positively with cyclin D1 overexpression and poor clinical outcome in head and neck squamous cell carcinoma

“…[36][37][38][39][40] We observed that HNSCC cells surrounding the cancer nest had elevated Abbreviations: CI, confidence interval; EZH2, enhancer of zeste homolog 2; HR, hazard ratio; pN, pathologic lymph node status; TNM, tumor-lymph node-metastasis classification.…”