Department of Internal Medicine, Hanyang University College of Medicine, Gyunggi-do, Korea.
APMIS. 2010 Mar;118(3):196-202. doi: 10.1111/j.1600-0463.2009.02579.x.
The enhancer of zeste homolog 2 (EZH2), a member of the polycomb group of proteins, plays an important role in cell proliferation and cell cycle regulation. EZH2 is overexpressed in aggressive forms of prostate, breast, bladder, and endometrial cancers. However, the role of EZH2 expression in gastric cancer has not been fully determined. This study was conducted to investigate the correlation between EZH2 and cell cycle-related molecules, and the clinical value of EZH2 expression in gastric cancer. We analyzed EZH2 expression using Western blotting in AGS, MKN-28, SNU-16, SNU-484, SNU-601, and SNU-638 gastric cancer cell lines. After transfection of EZH2 siRNA into MKN-28 cells, the change in cell cycle-related molecules was assessed by Western blot analysis. Expression of EZH2, Ki-67, and p53 was determined by immunohistochemical staining of tissue microarrays from specimens of 137 cases of resected gastric cancer. We found high expressions of EZH2 in all of the tested gastric cancer cell lines. RNA interference of EZH2 induced upregulation of p53 and HDAC1 and downregulation of cyclin D1 and cyclin E. High EZH2 expression was observed in 60.6% of gastric cancers and in 6.7% of non-neoplastic gastric tissues (p < 0.01); 40.1% were positive for p53 in gastric cancers. High EZH2 expression was correlated with Ki-67 and p53 expressions and was significantly associated with distant metastases and non-signet ring cells. Our results suggest that high EZH2 expression is associated with tumor cell proliferation and metastasis in gastric cancer.
增强子结合锌指蛋白 2（EZH2）是多梳蛋白家族的一员，在细胞增殖和细胞周期调控中发挥重要作用。EZH2 在侵袭性前列腺癌、乳腺癌、膀胱癌和子宫内膜癌中过表达。然而，EZH2 表达在胃癌中的作用尚未完全确定。本研究旨在探讨 EZH2 与细胞周期相关分子的相关性，以及 EZH2 在胃癌中的表达的临床价值。我们使用 Western blot 分析了 AGS、MKN-28、SNU-16、SNU-484、SNU-601 和 SNU-638 胃癌细胞系中 EZH2 的表达。在 MKN-28 细胞中转染 EZH2 siRNA 后，通过 Western blot 分析评估细胞周期相关分子的变化。通过对 137 例胃癌切除标本组织微阵列的免疫组织化学染色，检测 EZH2、Ki-67 和 p53 的表达。我们发现 EZH2 在所有检测的胃癌细胞系中均高表达。EZH2 的 RNA 干扰诱导 p53 和 HDAC1 的上调以及 cyclin D1 和 cyclin E 的下调。在 60.6%的胃癌和 6.7%的非肿瘤性胃组织中观察到 EZH2 高表达（p < 0.01）；在胃癌中，40.1%为 p53 阳性。EZH2 高表达与 Ki-67 和 p53 表达相关，与远处转移和非印戒细胞显著相关。我们的结果表明，EZH2 高表达与胃癌中肿瘤细胞的增殖和转移有关。
