EZH2 regulates expression of p57 and contributes to progression of ovarian cancer in vitro and in vivo
EZH2 regulates expression of p57 and contributes to progression of ovarian cancer in vitro and in vivo
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DOI：
10.1111/j.1349-7006.2010.01836.x
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发表时间：
2011-03-01
期刊：
影响因子：
5.7
通讯作者：
Wang, Zehua
中科院分区：
文献类型：
--
作者：
Guo, Jianfeng;Cai, Jing;Wang, Zehua
为了明确EZH 2在卵巢肿瘤中的表达模式，探讨EZH 2在体内外肿瘤发生中的作用及机制，本研究检测了EZH 2和p57在正常、良性和恶性卵巢组织中的蛋白和mRNA表达，并采用shRNA技术敲低卵巢癌细胞中EZH 2的表达，建立了卵巢癌裸鼠移植瘤模型。结果发现EZH 2在卵巢肿瘤组织中过表达，在卵巢恶性肿瘤组织中表达最高，在不同病理类型/分级和国际妇产科联盟（FIGO）分期中EZH 2表达差异有统计学意义。卵巢组织中EZH 2表达与p57 mRNA水平呈负相关。此外，内源性EZH 2的抑制增加了p57的表达，降低了卵巢癌细胞的增殖和迁移。EZH 2的缺失抑制体内卵巢肿瘤形成。我们的研究结果表明，EZH 2基因作为一个癌基因在卵巢癌的肿瘤发生与抑制抑癌基因p57的可能机制。EZH 2是治疗卵巢癌的潜在治疗靶点。（Cancer Sci 2011; 102：530-539）
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. (Cancer Sci 2011; 102: 530-539)