EB病毒LMP1在鼻咽癌细胞系中上调EGFR表达  

Increase of EGFR expression by Epstein-Barr virus LMP1 in nasopharyngeal carcinoma cells

作　　者：王承兴[1] 李晓艳[1] 顾焕华[1] 邓锡云[1] 曹亚[1] 

机构地区：[1]湖南医科大学肿瘤研究所,长沙410078

出　　处：《中华肿瘤杂志》2001年第4期269-272,共4页Chinese Journal of Oncology

基　　金：国家重点基础研究发展规划(973)资助项目(G1998051201);国家自然科学基金重点资助项目(39830410);国家自然科学基金杰出青年基金资助项目(39525022)

摘　　要：目的　阐明LMP1在鼻咽癌 (nasopharyngealcarcinoma ,NPC)中对表皮生长因子受体(epidermalgrowthfactorreceptor,EGFR)的上调作用。方法　以稳定表达LMP1及其 3种突变体的NPC细胞系为材料 ,以瞬间转染方法将肿瘤坏死因子受体相关因子 (tumornecrosisfactorreceptor associatedfactor,TRAF) 1,2 ,3及其显性负性突变体导入稳定表达LMP1的NPC细胞系 ,用Westernblotting方法检查EGFR表达特征 ,以确定LMP1是否通过TRAF调控EGFR表达。在补加EGF无血清培养中 ,绘制HNE2 LMP1和HNE2 pSG5生长曲线 ,以了解LMP1诱导EGFR的功能效应。结果　在NPC细胞系中 ,LMP1通过TRAF1,2 ,3上调EGFR ,其中LMP1CTAR1(carboxyterminalactivatingregion1)介导该效应 ,与HNE2 pSG5细胞相比 ,在补加EGF无血清培养条件下 ,HNE2 LMP1细胞增殖较快。结论　LMP1CTAR1通过TRAF1,2 ,3上调EGFR ,可能在NPC发生中起着重要作用。Objective To investigate the effect of LMP1 on the expression of epidermal growth factor receptor (EGFR) in HNE2 LMP1 cells. Methods Stable transfectant HNE2 cell line expressing LMP1 (HNE2 LMP1) or its mutants (HNE2 del 187 351, HNE2 1 231, HNE2 1 187) were used as cell models. The expression of EGFR was detected by Western blot method. The charactristics of EGFR expression were analyzed when HNE2 LMP1 cells were transiently transfected with TRAF1, 2, 3 or TRAF1, 2, 3 dominant negative mutants (DN TRAF1, 2, 3). The growth characteristics of HNE2 LMP1 and vector controls were analyzed on serum free media suppplemented with EGF. Results Stable expression of LMP1 in HNE2 cells increased the expression of EGFR. LMP1 CTAR1 domain, being identical to the TRAF interaction domain, was essential to the induction of EGFR. The CTAR2 domain did not induce expression of EGFR. Overexpression of either TRAF1, 3 or an dominant negative mutant of TRAF1, 3 inhibited the expression of EGFR, while TRAF2 or negative mutants of TRAF2 did slightly so. In HNE2 LMP1 cells, LMP1 expression increased the proliferative response to EGF while the vector control cells exhibited very low level of viability and did not proliferate. Conclusion The induction of EGFR by LMP1 CTAR1 may be an important component of EBV infection via an TRAF1, 2, 3 mechanism in the epithelial cells and may contribute to the development of epithelial malignancies such as nasopharyngeal carcinoma.

关 键 词：鼻咽肿瘤 EB病毒 表皮生长因子受体 

分 类 号：R739.63[医药卫生—肿瘤]