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乙肝病毒x蛋白激活缺氧诱导因子-1通路促进血管内皮生长因子表达的研究 被引量:12

Hepatitis B x protein activated vascular endothelial growth factor expression through hypoxia inducible factor-1 pathway
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摘要 目的 探讨乙肝病毒x蛋白 (HBx)是否可以通过激活缺氧诱导因子 1α(HIF 1α)通路促进血管内皮生长因子 (VEGF)的表达。方法 将pIRES EGFP HBx和pTK Hyg质粒共同转染人肝癌细胞系SMMC 772 1,筛选出荧光阳性和阴性的抗性克隆 ,检测两种克隆中VEGF和HIF 1α在mRNA和蛋白水平的表达。结果 荧光阳性细胞有HBx的稳定整合和表达 ,并有HIF 1α和VEGF的上调表达 ;荧光阴性细胞无HBx的表达 ,HIF 1α和VEGF的表达亦为阴性。结论 HBx可以通过激活HIF 1通路促进VEGF的表达。 Objective To invesigate whether hepatitis B x protein(HBx) stimulates vascular endothelial growth factor (VEGF) through hypoxia inducible factor-1(HIF-1α) pathway. Methods Two plasmids including pIRES-EGFP-HBx and pTK-Hyg were co-transfected to a hepatocellular carcinoma cell line SMMC-7721. With fluorescence-positive and fluorescence-negative hygromycin-resistant colonies selected, expressions of VEGF and HIF-1α in protein or/and mRNA level were detected. Results Fluorescence-positive cells were stably integrated with HBx,in which expression of HIF-1α and VEGF were upregulated. Fluorescence-negative cells did not express HBx, VEGF or HIF-1α. Conclusion HBx can activate VEGF through HIF-1α pathway.
出处 《中华肿瘤杂志》 CAS CSCD 北大核心 2003年第5期433-436,共4页 Chinese Journal of Oncology
基金 教育部高等学校博士学科点专项科研基金资助项目(2 0 0 3 0 4870 5 9)
关键词 乙肝病毒X蛋白 激活 缺氧诱导因子-1 血管内皮生长因子 表达 研究 肝肿瘤 Liver neoplasms Hepatitis B viru x protein Vascular endothelial grouth factor HIF-1
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  • 1丁磊 陈孝平 王海平.反义封闭HIF-1和Smad 作用位点对VEGF表达的影响[J].中华实验外科杂志,2002,19:78-79.
  • 2Lee SW, Lee YM, Bae SK. Human hepatitis B virus X protein is a possible mediator of hypoxia-induced angiogenesis in hepatocarcinogeresis Biochem Biophys Res Commun, 2000,268:456:461.
  • 3Panu J, David RM, Tian YM, et al. Targeting of HIF-α to the von hippel-lindau ubiquitylationcomplex by O2-regulated prolyl hydroxylation.Science.2001.292:468-472.
  • 4Michael JB, Wang LH. Calcium signaling by HBx protein in hepatitis B virus DNA replication. Science,2001,294:2376.
  • 5Huang J, Kwong J, Sun EC, et al. Proteasome complex as a potential cellular target of hepatitis B virus X protein. J Virol, 1996, 70: 5582-5591.
  • 6Tilman SE, Luisa MB, Beatriz V, et al. Synergistic cooperation between hypoxia and transforming growth factor-β pathways on human vasatlar endothelial growth factor gene expression. J Biol Chem,2001,276:38527-38535.

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