STATs信号传导通路成员选择性活化与结直肠癌发生机制的研究

Mechanism of selective activation of STATs signal transduction pathway and its association with colorectal carcinomas

目的检测STATs信号传导通路重要成员在结直肠癌组织中的表达与活化,分析STATs成员与结直肠癌临床病理特征的关系。方法应用Westernblot检测结直肠癌组织中Stat1、Stat3、Stat5及其下游产物cyclin D1、Bcl-xL的表达,免疫组织化学法检测STATs成员在细胞水平的分布。结果结直肠癌组织中STATs信号传导通路成员Stat3、Stat5及其下游产物cyclin D1、Bcl-xL蛋白表达水平明显高于正常肠黏膜(P<0.05);p-Stat3、p!Stat5表达水平与TNM分期较晚(Ⅲ/Ⅳ)及淋巴结转移有关(P<0.05),cyclin D1与淋巴结转移有关(P<0.05),p-Stat3与cyclinD1在结直肠癌组织中表达情况呈线性相关,相关系数为0.480(P<0.05)。结论STATs信号传导通路持续活化可能在结直肠癌的发生中起重要作用,其详细作用机制还需要进一步研究。

Objective The purpose of this study was conducted to investigate the role of key members of STATs and its downstream mediators in carcinogenesis of colorectal carcinoma. Methods Tissue samples from 45 patients with colorectal carcinoma were tested for representing various clinicopathological parameters, Statl, Stat3, Stat5 and downstream mediators cyclin D1, Bcl-XL expression by Western blot analysis. Results STATs and its downstream mediators cyclin D1 and Bcl-xL protein level were increased in colorectal cancer patients compared with adjacent normal mucosa （P〈0.05）, it was found that overexpression of p-Stat3, p-Stat5 was related to TNM stage and lymph nodes involvement in colorectal cancer （P〈0.05）. It was also found that cyclin D1 was in a positive correlation fashion with p-Stat3 in colorectal carcinoma （P〈 0.05）. Conclusions This study has shown that abnormal activation of STATs signaling plays an important role in the carcinogenesis of colorectal carcinoma. Its possible mechanism needs further investigation.