N—cadherin、β-连环素在肝癌组织中的表达及与Wnt信号途径的关系

The expressions of N-cadherin and β-catenin in hepatocellular carcinoma and its correlation with Wnt signaling pathway

目的观察肝癌（HCC）中N—cadherin分子是否调控β-连环素（β-catenin）的表达及Wnt信号途径的活化。方法免疫组织化学分析64例肝癌组织中N—cadherin及p-catenin的表达及相互关系。调控肝癌细胞株HCCLM3、SMMC-7721中N—cadherin表达并检测β-catenin的表达及Wnt信号途径的活化。结果64例肝癌中，N—cadherin表达缺失34例；β-catenin在细胞膜上表达，无细胞核内聚集，且13例细胞膜表达缺失；细胞膜上β-catenin表达缺失与N—cadherin表达缺失呈正相关（P〈0．05）。下调HCCLM3细胞或上调SMMC-7721细胞中的N—cadherin表达导致细胞膜上β-catenin表达减弱或增强，但均未导致Wnt信号途径的活化。结论在肝癌中，N—cadherin表达与细胞膜上β-catenin的表达水平呈正相关，但N—cadherin分子并不参与Wnt信号途径的调控。

Objective To＇investigate whether N-cadherin modulates expression of β-catenin and activation of the Wnt signaling pathway in hepatocellular carcinoma （ HCC ）. Methods The expressions of N-cadherin and β-catenin in 64 HCC tissues were measured by immunohistochemistry and the relationship between them was studied. Furthermore, N-cadherin expression in HCC cell lines, HCCLM3 and SMMC-7721 cells,was regulated and its effect on expression of β-catenin and activity of Wnt singnaling pathway was evaluated. Results Among the 64 HCCs examined,34 HCCs showed reduced N-cadherin expression;β-catenin staining was observed on cell membranes but not in cell nuclei and 13 HCCs showed reduced membranous staining;the reduced expression of β-catenin on cell membranes was correlated with reduced N-cadherin expression （P 〈 0. 05 ）. Down-regulation of N-cadherin in HCCLM3 ceils resulted in reduced membranous β-catenin expression but not activation of the Wnt signaling pathway. In contrast ,up-regulation of N-cadherin expression in SMMC-7721 ceils led to increased expression of membranous β-catenin but had no effect on Wnt signaling pathway. Conclusion In HCC,the level of N-cadherin was positively correlated with membranous β-eatenin expression;however, N-eadherin was not involved in regulation of the Wnt signaling pathway.