Department of Obstetrics and Gynecology, Tongji Medical College, Union Hospital, Huazhong University of Science and Technology, Wuhan, China.
Cancer Sci. 2011 Mar;102(3):530-9. doi: 10.1111/j.1349-7006.2010.01836.x. Epub 2011 Jan 18.
In order to determine the expression pattern of EZH2 in ovarian neoplasms and assess the functions and mechanism of EZH2 in tumorigenesis in vitro and in vivo, we detected the protein and mRNA expression of EZH2 and p57 in normal, benign and malignant ovarian tissues, used shRNA to knock down EZH2 expression in ovarian cancer cells and established a nude mouse xenograft model. We found EZH2 was overexpressed in ovarian tumor with the highest level expression in malignant ovarian tissues, and the variation of EZH2 expression at different pathological type/grade and International Federation of Gynecology and Obstetrics (FIGO) stages was statistically significant. Furthermore, the EZH2 expression was inversely correlated with the p57 mRNA level in ovarian tissues. Moreover, inhibition of endogenous EZH2 increased the expression of p57 and reduced proliferation and migration of ovarian cancer cells. Loss of EZH2 suppresses ovarian tumor formation in vivo. Our results indicate that the EZH2 gene acts as an oncogene in tumorigenesis of ovarian cancer with the possible mechanism to suppress the anti-oncogene p57. EZH2 is a potential therapeutic target for treatment of ovarian cancer.
为了确定 EZH2 在卵巢肿瘤中的表达模式，并评估 EZH2 在体外和体内肿瘤发生中的功能和机制，我们检测了正常、良性和恶性卵巢组织中 EZH2 和 p57 的蛋白和 mRNA 表达，使用 shRNA 敲低卵巢癌细胞中的 EZH2 表达，并建立了裸鼠异种移植模型。我们发现 EZH2 在卵巢肿瘤中过度表达，在恶性卵巢组织中表达水平最高，EZH2 表达在不同病理类型/分级和国际妇产科联合会（FIGO）分期的变化具有统计学意义。此外，EZH2 的表达与卵巢组织中 p57 mRNA 水平呈负相关。此外，抑制内源性 EZH2 增加了 p57 的表达，并降低了卵巢癌细胞的增殖和迁移。EZH2 的缺失抑制了体内卵巢肿瘤的形成。我们的研究结果表明，EZH2 基因在卵巢癌的肿瘤发生中作为一种癌基因发挥作用，其可能的机制是抑制抑癌基因 p57。EZH2 是治疗卵巢癌的潜在治疗靶点。
