丙型肝炎病毒核心蛋白对胞外基质金属蛋白酶诱导物基因转录的影响  

Effect of HCV Core Protein on the Gene Transcription of Extracellular Matrix Metalloproteinase Inducer

作　　者：冯晓燕[1] 郭兰芹[1,2] 贺锋[1] 许立博[1,3] 宋晓国[1] 张贺秋[1] 

机构地区：[1]军事医学科学院基础医学研究所,北京100850 [2]华北石油总医院,河北任丘062552 [3]沈阳农业大学,辽宁沈阳110161

出　　处：《生物技术通讯》2009年第2期166-168,172,共4页Letters in Biotechnology

基　　金：国家自然科学基金(30600308);国家"十一五"重大专项(2008ZX10002-013);"十一五"全军医药卫生科研基金(06MA319)

摘　　要：目的:探讨丙型肝炎病毒(HCV)核心蛋白对胞外基质金属蛋白酶诱导物(EMMPRIN)基因转录的影响。方法:构建HCV核心蛋白真核表达载体和EMMPRIN启动子删除突变体pGL3载体,应用双萤光素酶报告基因系统检测EMMPRIN启动子不同删除突变体的转录活性,并寻找核心蛋白上调EMMPRIN转录相关的关键启动子区段。结果:HCV核心蛋白可以显著上调EMMPRIN的表达;调节EMMPRIN转录的启动子关键区段为+1～435bp,HCV核心蛋白主要通过该关键区段上调EMMPRIN的转录,并呈现剂量依赖性。结论:HCV核心蛋白有可能通过EMMPRIN启动子关键区段上调EMMPRIN的转录,从而上调基质金属蛋白酶,最终导致肝癌转移。Objective： To investigate the effect of HCV core protein on the gene transcription of extracellular matrix metalloproteinase inducer（EMMPRIN）. Methods： The eukaryotic expression vector containing the HCV core gene and the series of pGL3 vectors containing different length promoter sequences of EMMPRIN were constructed. The transcriptional activities of different length promoter of EMMPRIN were detected using the dual-luciferase reporter assay, and the important promoter region in related to the up-regulation of the transcription of EMMPRIN by HCV core protein was found. Results： The expression of EMMPRIN was up-regulated by core protein significantly. HCV core protein up-regulated the transcription of EMMPRIN mainly through the promoter region ＋1-435 bp, which play a key role in the transcription of EMMPRIN. The up-regulation of core protein on the transcription of EMMPRIN showed dose dependent. Conclusion： The transcription of EMMPRIN was up-regulated by HCV core protein through the promoter region ＋1-435 bp, thereby the expression of matrix metalloproteinase were up-regulated, and in the final, inducing the metastasis of hepatoma.

关 键 词：丙型肝炎病毒核心蛋白 胞外基质金属蛋白酶诱导物 双萤光素酶报告基因系统 转录 

分 类 号：Q78[生物学—分子生物学]