δ-catenin对非小细胞肺癌凋亡的影响及其机制初探

项目名称： δ-catenin对非小细胞肺癌凋亡的影响及其机制初探

项目编号： No.81201844

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学2

项目作者： 张俊毅

作者单位： 赤峰学院

项目金额： 23万元

中文摘要： 我们最新的研究显示，p120ctn亚家族中的δ-catenin蛋白在肺癌中表达增高并与患者的不良预后显著相关；此外，过表达δ-catenin通过调节小GTPases酶的活性而促进肺癌细胞的恶性表型。有文献显示JNK通过使δ-catenin磷酸化而促进后者的降解并介导了神经元的凋亡，我们的预实验也发现过表达δ-catenin显著抑制了肿瘤细胞的凋亡，因此我们提出δ-catenin可能通过抑制JNK通路的活性而抑制肿瘤细胞的凋亡。我们拟首先在肺癌组织中借助免疫组化和TUNEL方法分别检测δ-catenin的表达和细胞凋亡情况，然后在肺癌细胞系中检测过表达或干扰δ-catenin前后JNK活性和瘤细胞凋亡情况的改变，并在实验过程中借助JNK的特异性抑制剂和激活剂进一步证明该通路在δ-catenin调节肿瘤细胞凋亡过程中发挥主要作用。此外，我们也将通过裸鼠种植实验来验证体外实验的结果。

中文关键词： δ-catenin；肺癌；细胞凋亡；；

英文摘要： Our latest research indicated that,δ-catenin, a member of p120ctn sub-family, was higher expression in lung cancer, and its higher expression was closly associated with poor prognosis of patients. Moreover,δ-catenin overexpression promoted malignant phenotype of lung cancer cells through regulating the activities of small GTPases. It was reported that JNK could phosphorylate δ -catenin and promoted its degradation, at the same time JNK also mediated neuronic apoptosis. Furthermore, our pilot study revealed that δ-catenin overexpression inhibited the apoptosis of tumor cells. So, this raises the possibility that δ -catenin can inhibit the apoptosis of tumor cells through restraining the activity of JNK pathway. In this study, we plan to examine the expression of δ-catenin and the apoptosis in lung cancer tissues via immunohistochemistry and TUNEL methods, respectively. In addition, we also observe the changes of JNK activity and apoptosis before and after up/down-regulating δ-catenin in lung cancer cells. At the same time, we will further to prove the important role of JNK involved in δ-catenin regulating apoptosis by means of specific inhibitor and stimulator of JNK pathway. Moreover, we will confirm the results derived from in vitro study with xenograft to nude mice.

英文关键词： δ-catenin；lung cancer；cell apoptosis；；