鼻咽癌中EB病毒潜伏膜蛋白1对p53表达的调控  

EBV latent membrane protein 1 induces p53 expression via NF-κB in nasopharyngeal carcinoma

作　　者：廖伟[1] 唐敏[1] 殷莉群[1] 邓锡云[1] 曹亚[1] 

机构地区：[1]湖南医科大学肿瘤研究所分子生物研究室,长沙410078

出　　处：《中华肿瘤杂志》2001年第3期199-201,共3页Chinese Journal of Oncology

基　　金：国家自然科学基金资助项目(39700170,39970820);国家重点基础研究发展规划资助项目(G1998051201);美国中华医学基金资助项目(CMB96655)

摘　　要：目的　探讨EB病毒潜伏膜蛋白 1(LMP1)是否通过NF κB在鼻咽癌细胞中促进p5 3蛋白的表达 ,为阐明LMP1促进细胞凋亡的机制提供实验依据。方法　利用四环素诱导表达系统 ,建立受四环素调控表达LMP1的鼻咽癌细胞系。用报道基因检测法和Western印迹技术 ,观察LMP1过量表达对NF κB的功能性活化及p5 3、bcl 2表达的影响。结果　在鼻咽癌细胞中 ,LMP1能活化NF κB。过量表达的LMP1促进p5 3基因的表达 ,这种促表达可以被硫代磷酸化修饰的LMP1及p6 5反义寡聚脱氧核苷酸阻断。LMP1和p6 5对bcl 2的表达则没有影响 ,LMP1过表达对bcl 2的表达无影响。结论鼻咽癌中LMP1通过活化核转录因子NF κB调节p5 3的表达 ;而在LMP1过表达时 ,bcl 2介导的抗凋亡机制未被启动 ,至少是未被上调的。Objective To ascertain if EBV encoded latent membrane protein 1 (LMP1) induces p53 expression via NF κB signaling.Methods A nasopharyngeal carcinoma cell line, Tet on LMP1 HNE2, transfected with LMP1,the expression of which was regulated by tetracycline, was used in this study. Functional activity of NF κB was determined by luciferase reporter assay and expression of p53 and bcl 2 was detected by Western blot.Results LMP1 induced p53 expression via NF κB signaling pathway. Induction of p53 expression could be blocked by phosphorothiate analogs of antisense oligonucleotides to NF κB p65 and LMP1, but not by NF κB p50. However, it seemed that LMP1 had no influence on bcl 2 expression in nasopharyngeal carcinoma.Conclusion Induction expression of p53 by EBV encoded LMP1 implies that p53 may act as a mediator in apoptosis triggered by LMP1, which brings about a complex balance in nasopharngeal carcinogenesis.

关 键 词：鼻咽肿瘤 爱泊斯坦一巴尔病毒 潜伏膜蛋白1 P53基因 

分 类 号：R739.63[医药卫生—肿瘤] R730.231[医药卫生—临床医学]