肾癌中E-cadherin甲基化状态的检测及其与β-catenin表达的关系

摘要

Objective:To investigate the relationship between the methylation status of E-cadherin gene andβ-catenin expression in renal cell carcinoma. Methods:Methylation specific PCR( MSP)method was used to examine the methylation status of E-cadherin gene in tumors and corresponding non-cancerous renal tissue. Immunohisto-chemistry was used to examine the expression of E-cadherin andβ-catenin in 53 specimens of renal cell carcinoma tissue and 53 specimens of adjacent non -tumor renal tissue. Results:Between gene level and protein level,there were negative correlations between E-cadherin gene methylation and expression of β-catenin protein in renal cell carcinoma tissues(r= -0. 361,P﹤0. 05). There was a positive correlation between E-cadherin protein and β-catenin protein in renal cell carcinoma tissues(r=0. 716,P﹤0. 001). Between gene level and protein level,there were negative correlations between E-cadherin gene methylation and expression of E-cadherin protein in renal cell carcinoma tissues(r= -0. 296,P﹤0. 05). Conclusion:E-cadherin and β-catenin maybe collectively participa-ted in a series of pathological progression( tumorigenesis,progression,invasion and metastasis)of renal cell carcino-ma. Besides participating cell adhesion,E-cadherin might interact with Wnt signaling pathway. It had effect on the invasion and metastasis of renal cell carcinoma through changing the intracellular distribution ofβ-catenin. It indica-ted that this signaling pathway was involved in tumorigenesis.%目的：研究肾癌（ renal cell carcinoma，RCC）中E-钙黏蛋白（ E-cadherin）甲基化状态的检测及其与β-链蛋白（β-catenin）表达的关系。方法：应用甲基化特异性聚合酶链反应（ methylation specific PCR，MSP）技术检测53例肾癌组织及相应癌旁正常组织中E-cadherin基因的甲基化状态。免疫组织化学SP法检测53例肾癌组织及相应癌旁正常组织中E-cadherin和β-catenin蛋白的表达。结果：在基因水平和蛋白水平，E-cadherin甲基化与β-catenin的蛋白表达呈负相关（ r=-0.361，P﹤0.05）；在蛋白水平，E-cadherin与β-catenin呈正相关（ r=0.716，P﹤0.001），在基因水平和蛋白水平，E-cadherin甲基化与蛋白表达呈负相关（r=-0.296，P﹤0.05）。结论：E-cadherin和β-catenin可能共同参与了包括肾癌的发生、发展、侵袭、转移等一系列病理过程。肾癌组织E-cadherin基因甲基化的发生可能与β-catenin抑制表达有关，可通过β-catenin与Wnt传导通路产生交互协同作用，影响β-catenin的细胞内分布，共同影响肾癌的侵袭转移进程。同时，提示Wnt通路在肾癌中处于激活状态，表明该传导通路的异常激活与肾癌的发生关系密切。