JNK相互作用蛋白通过JNK途径影响鼻咽癌的增殖和凋亡(英文)  

Effect of JIP on The Proliferation and Apoptosis of Nasopharyngeal Carcinoma Cells Through Interaction With JNK Mediated Pathway

作　　者：胡智[1] 陶永光[1] 唐发清[1] 杨力芳[1] 赵燕[1] 曾亮[1] 罗非君[1] 曹亚[1] 

机构地区：[1]中南大学湘雅医学院肿瘤研究所,长沙410078

出　　处：《生物化学与生物物理进展》2003年第4期579-585,共7页Progress In Biochemistry and Biophysics

基　　金：国家重点基础研究发展规划项目 (973 ) (G19980 5 12 0 1);国家自然科学基金资助项目 (3 0 0 0 0 0 87)~~

摘　　要：EB病毒编码的瘤蛋白潜伏膜蛋白 (LMP1)所介导的活化蛋白 (AP 1)信号转导途径在细胞增殖、分化、转化与凋亡方面发挥着重要作用 .越来越多的证据表明 ,AP 1信号转导通路中上游激酶JNK在鼻咽癌的发生发展过程中起着重要作用 .最近克隆出来的JNK相互作用蛋白 (JIP 1)是一种能抑制JNK核移位的胞浆锚蛋白 .为探讨JIP在LMP1调控AP 1信号通路中的作用机制 ,采用间接免疫荧光法和报告基因法 ,发现JIP通过有效地抑制磷酸化的JNK从胞浆移位入核 ,从而抑制LMP1上调的AP 1活性 .同时 ,JIP导入鼻咽癌细胞中 ,MTT法发现JIP能够明显抑制鼻咽癌细胞的生长 .进一步发现转染JIP后细胞的集落形成率与对照组相比大约降低了 5 3 6 % ,也抑制了细胞 .提示JIP可明显抑制细胞的增殖作用 .进一步采用流式细胞术分析 ,结果发现JIP引起细胞G1/S期细胞阻滞 ,说明JIP是抑制细胞增殖的重要调节子 .进一步采用流式细胞术定量发现 ,转染JIP后细胞的 2 4h凋亡百分率由 1 2 5 %上升到 8 2 5 % ,上升约 6 6倍 ,4 8h由 1 0 4 %上升到 31 4 5 % ,上升约 30倍 .采用激光共聚焦显微镜发现 ,转染JIP后细胞核发生显著变化 ,核质由均匀状态固缩成高凝集状态 ,形成了典型的胞膜体 .提示JIP可有效地促进细胞凋亡 .结果表明 ,JIP可通过抑制活化的JNK?Activator protein 1 (AP-1) is known to be constitutively activated by the Epstein-Barr latent membrane protein I in nasopharyngeal. carcinoma cells. Increasing evidence indicated that C-jun N-terminal kinase (JNK), the key upstream kinase of AP-1 mediated signal transduction pathway, plays a key role in the carcinogenesis and progression of nasopharyngeal carcinoma. JNK interacting protein 1 (JIP-1) was newly identified as a potent inhibitor of JNK. The effect of JIP on the proliferation of nasopharyngeal carcinoma cells through interaction with the AP-1 signaling pathway was detected using immunofluroscence, reporter gene, MTT, colony formation and flow cytometric analysis. In nasopharyngeal carcinoma cells, data suggested that JIP down-regulated AP-1 activity through the inhibition of the translocation of phospho-JNK from the cytoplasm to the nucleus. Furthermore, JIP inhibited the rates of cell survival and colony formation. The number of cells in S phase decreased and the number of cells in G1/G0 phase increased after the flow cytometric analysis, suggesting that JIP induced growth arrest of Teton-LMP1-HNE2 cells in G1/S phase of the cell cycle. The results, therefore, demonstrated that JIP, by inhibiting AP-1-mediated signal transduction pathway, interfered the cell cycle and may act as an important negative regulator of the proliferation of nasopharyngeal carcinoma cells. Also, it was detected by flow cytometry analysis and laser scanning confocal microscope that JIP triggered the apoptosis of NPC cells. In conclusion, JIP represents a promising new therapeutic molecule for nasopharyngeal carcinoma.

关 键 词：JNK 蛋白 鼻咽癌 增殖 凋亡 瘤蛋白潜伏膜蛋白 信号转导 细胞增殖 

分 类 号：R739.6[医药卫生—肿瘤] Q253[医药卫生—临床医学]