c-Met在人乳腺癌组织中的表达及其与明胶酶的关系

Clinical impact of c-Met and its relationship with gelatinase in human breast cancer

目的研究c-Met蛋白在人乳腺癌组织中的表达及其临床意义,探讨其与乳腺癌明胶酶(MMP-2和MMP-9)关系。方法应用免疫组织化学方法检测86例乳腺癌组织c-Met蛋白的表达情况,分析它们与患者临床病理特征和预后的关系;使用siRNA技术特异性下调乳腺癌细胞内源性c-Met后,western blot方法检测乳腺癌细胞MMP-2和MMP-9表达水平。结果人乳腺癌c-Met蛋白表达阳性率为58.1%,其表达与肿瘤淋巴结转移和临床分期均呈显著正相关(P<0.01),与患者总生存期和无复发生存期均呈负相关(P<0.01);相关性分析显示:乳腺癌c-Met和MMP-2及MMP-9表达均呈显著正相关(r=0.314和0.322,P<0.01);使用siRNA特异性下调乳腺癌MDA-MB-231细胞c-Met表达后,MMP-2和MMP-9表达也显著降低。结论乳腺癌c-Met表达状况与侵袭转移密切相关,其功能可能是通过调控MMP-2和MMP-9表达而发挥作用。

Objective To investigate the clinical significance of c-Met in human breast cancer, and the relationship between c-Met and gelatinase （MMP-2 and MMP-9）. Methods The expression of c-Met pro- tein was detected in 86 cases of breast cancer by immunohistochemistry. The expression of MMP-2 and MMP-9 in breast cancer cells was examined after transfection with c-Met siRNA by western blot assay. Results The positive rate of c-Met protein was 58.1~ in breast cancer, which was significantly correlated to lymph node metastasis, clinical stage and patient survival（P^0. 01）. A significant correlation was found between the expression of c-Met and gelatinase protein in breast cancer（r=0. 314 and 0. 322,P〈0. 01）. The expression of gelatinase was significantly downregulated by transfeetion with c-Met siRNA in MDA-MB-231 cells, compared with that of controls. Conclusion The c-Met plays an important role in breast cancer invasion and metastasis by partly regulating the expression of gelatinase.