细胞外调节蛋白激酶信号通路在乙型肝炎病毒X基因调控c-met基因启动子中的作用  

Hepatitis B virus X protein regulates c-met promoter via the ERKs singal pathway in HepG2 cells

作　　者：谢斌[1] 唐春[1] 陈平[1] 苟元斌[1] 袁涛[1] 金世龙[1] 周渝阳[1] 

机构地区：[1]第三军跃大学大坪医院野战外科研究所肝胆外科,重庆400042

出　　处：《中华肝脏病杂志》2009年第7期531-534,共4页Chinese Journal of Hepatology

基　　金：重庆市科学技术委员会自然科学基金（CSTC2006BB5107）

摘　　要：目的明确在乙型肝炎病毒X基因（HBx）对原癌蛋白质（c-met）基因启动子区的调控中所涉及的信号传导通路及其在肝癌侵袭和转移中的作用。方法用Western blot比较可能涉及的信号通路特异性阻断剂对HBx调控c-met表达的影响，分析在该调控过程中所涉及的信号通路。体外侵袭试验验证信号传导通路在HBx调控c-met表达中的作用。对数据进行析因设计的方差分析。结果HBx引起c-met表达水平的增加，细胞外调节蛋白激酶信号通路抑制剂U0126能够降低该作用，而D38MAPK信号通路抑制剂SB203580、PI-3K信号通路抑制剂wortmanin则未显示出该作用。体外细胞侵袭试验也证实了U0126能够降低HBx引起的HepG2细胞的强侵袭性[（74．3±6．2）个与（34．6±5．2）个，F=113．45，P〈0．01】。结论HBx引起肝癌细胞的侵袭转移可能与其通过细胞外调节蛋白激酶信号通路对c-met基因启动子区（-183bp～-100bp）的调控有关。Objective To explore the signal pathway mediating the regulatory effect of Hepatitis B virus X protein （HBX） on c-met gene promoter in HepG2 cells. Methods The expression of c-met in HBX- transfected HepG2 cells treated with different signal pathway inhibitors was detected by western blot, the invasion capability of cells was determined by Matrigel invasion assay. Results ERK inhibitor U0126 inhibited the expression of the c-Met in HBx-transfected HepG2 cells. However, both p38MAPK inhibitor SB203580 and PI-3K inhibitor wortmanin had no effect on expression of the c-Met in HBx-transfected HepG2 ceils. Furthermore, the ERK inhibitor U0126 also inhibited the invasiveness of HBX-transfected HepG2 cells. Conclusion HBx induces invasion of HCC via activation of ERK pathway.

关 键 词：癌 肝细胞 X蛋白 肝炎病毒 乙型 原癌蛋白质c-met 细胞外调节蛋白激酶 信号通路 

分 类 号：R686[医药卫生—骨科学]