连接蛋白43在肺癌组织中表达及对E-cadherin的影响

Expression of connexin 43 in lung cancer and its correlation with E-cadherin

目的探讨连接蛋白(Cx)43和E-cadherin蛋白在肺癌中表达及两者关联性,研究Cx43对E-cadherin表达的影响。方法采用免疫组织化学SP法检测85例原发性肺腺癌、鳞癌组织中Cx43和E-cadherin蛋白表达,分析两者的相关性;采用Cx43基因转染人肺巨细胞癌LH7细胞,分析转染Cx43后对E-cadherin蛋白表达以及对细胞生长速度和细胞周期的影响。结果Cx43和E-cadherin蛋白在癌旁肺组织中均呈膜阳性表达,而在肺癌组织中表达下降,其阳性率分别为50·6%和67·1%,且两者表达下降存在关联性。Cx43和E-cadherin蛋白的表达下降程度与肺癌的分化程度、P-TNM分期和淋巴结转移正相关。LH7细胞转染Cx43基因后,Cx43蛋白表达增加的同时,E-cadherin蛋白也表达升高,且两者均为胞质表达,未见明确的细胞膜表达;转染Cx43基因后细胞增殖速度减慢,与对照组相比,G1期细胞增多,而S、G2期细胞数目减少。结论Cx43和E-cadherin蛋白在肺癌组织中表达下降,且两者之间存在关联性,表达下降程度与临床病理参数相关;LH7细胞转染Cx43基因后,在出现胞质Cx43表达增加的同时,可诱导E-cadherin的胞质表达;Cx43可通过参与细胞周期调节抑制细胞生长速度。

Objective To investigate the expression of connexin 43 and E-cadherin in lung cancer and to study the interaction between the two molecules. Methods The expression and correlation of connexin 43 and E-cadherin were evaluated by immunohistochemistry （S-P method ） in 85 samples of primary squamous cell carcinoma and adenocarcinoma of the lung. In addition, connexin 43 expression vector was transfected into the lung giant cell carcinoma cell line LH7 followed by analyses of connexin 43 and E-cadherin expressions, the growth rates and cell cycle profiles of the transfected cells. Results Comparing with the adjacent non-neoplastic lung tissue, expression of connexin 43 and E-cadherin was decreased in a correlative fashion in beth squamons cell carcinomas and adenocarcinomas. Their expression reversely correlated to the degree of tumor cell differentiation, P-TNM stage, and status of lymph note metastasis. The expression of connexin 43 and E-cadherin increased significantly after transfection of connexin 43 expression vector into the LH7 cells （ P〈0.05 ）. Both expressions were limited in the cytoplasm before or after the transfection. The proliferation rate of LH7 cells was signiilcanfly decreased by connexin43 expression （ P〈0.05 ）, along with an increase of cell population at G1 phase and a decrease of percentage of cells in S and G2 phases （P〈0.05 ）. Conclusions Squamous cell carcinoma and adenocarcinoma of lung have a low level of connexin 43 and E-cadherin expression, which are correlated with the clinicopathologic features of the tumors. Transfection expression of conner, in 43 gene induces an E-cadherin overexpression and an inhibition of LH7 cell proliferation indicating the significant role of onnexin 43 in the regulation of cell proliferation.