Syk基因对乳腺癌血管内皮生长因子-C表达的调控作用

Regulatory role of Syk gene on vascular endothelial growth factor C expression in breast cancer

目的 研究Syk基因对乳腺癌血管内皮生长因子（VEGF）-C表达的调控机制.方法 采用免疫组织化学（EnVision法）检测乳腺癌组织中Syk、NFκB与VEGF-C的蛋白表达情况,分析三者的相关性及与淋巴转移的关系.转染pcDNA3.1（-）-Syk至乳腺癌MDA-MB-231细胞,检测对VEGF-C和NFκB表达的影响.结果 在淋巴转移组中,Syk蛋白阳性率低于非淋巴转移组,VEGF-C与NFκB阳性率在淋巴转移组高于非淋巴转移组.Syk蛋白表达与NFκB（r=-0.448,P=0.002）、VEGF-C（r=-0.620,P=0.000）蛋白表达呈负相关,VEGF-C与NFκB呈正相关（r =0.310,P=0.036）.转染pcDNA3.1（-）-Syk重组质粒的乳腺癌细胞中VEGF-C的mRNA及蛋白表达水平均低于空白对照组,细胞核NFκB蛋白表达低于空白对照组（均P＜0.05）.结论 Syk基因与乳腺癌转移相关,可能是通过抑制NFκB的活性而下调VEGF-C的表达,从而抑制乳腺癌的淋巴转移.

Objective To investigate the effect of Syk on the VEGF-C expression in breast cancer.Methods Immunohistochemical EnVision method was used to detect the protein expression of Syk,NFκBand VEGF-C in breast carcinoma; and the relationship between protein expression of Syk,NFκB,VEGF-C and lymph node metastasis was analysed.MDA-MB-231 cells were transfected with pcDNA3.1 （ - ）-Syk,and the effect of Syk gene on the VEGF-C and NFκB expression was determined.Results In the lymph node metastatic group,a lower expression rate of Syk and higher expression rate of VEGF-C and NFκB were detected as compared to the non-metastatic group.The expression of Syk was negatively associated with NFκB （r=-0.448,P=0.002） and VEGF-C （r=-0.620,P=0.000） expression,and VEGF-C was associated with the nuclear expression of NFκB （ r =0.310,P =0.036）.Compared with the non-transfected cells,the pcDNA3.1 （ -）-Syk transfected MDA-MB-231 cells showed significantly lower transcriptional level of VEGF-C mRNA,expression level of VEGF-C protein and NFκB activity （ P 〈 0.05 ）.Conclusions Syk may play an important role in the lymph node metastasis of breast cancer.It may down-regulate the expression of VEGF-C by inhibiting the activity of NFκB,which thus suppresses lymph node metastasis of breast cancer