Stimulation of B7-H1 in Hepatocarcinoma Cells by Hepatitis B virus X Antigen
Stimulation of B7-H1 in Hepatocarcinoma Cells by Hepatitis B virus X Antigen
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乙型肝炎病毒X抗原对肝癌细胞B7-H1的刺激
DOI：
10.3109/08820139.2010.494193
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发表时间：
2010-01
影响因子：
2.8
通讯作者：
Wu, Yuzhang
中科院分区：
文献类型：
--
作者：
Wu, Shengxi;Yang, Chengying;Guo, Sheng;Fei, Lei;Luo, Na;Fu, Xiaolan;Chen, Yongwen;Wu, Yuzhang
乙肝病毒X蛋白(HBx)和B7-H1在肝癌中的相互作用尚不清楚。本研究分析了HBx和B7-H1在肝癌发生中的潜在关系。人肝癌细胞系HepG2稳定表达HBx蛋白(HBx+-HepG2)。比较全基因组芯片分析(CapitalBio)和实时定量聚合酶链式反应(QPCR)证实，与对照载体(HBx-HepG2)相比，B7-H1mRNA在这些细胞中的转录显著增加。流式细胞仪和Western-blotting进一步证实HBx+-HepG2细胞B7-H1蛋白合成增强。启动子结构的定点突变表明，转录因子(NF)-κB结合位点位于B7-H1基因转录起始点上游128~137bp之间，是HBx介导的B7-H1表达的主要原因。与HBx+-HepG2/T细胞共培养实验表明，T细胞的凋亡数显著增加，加入抗B7-H1的中和性单抗可部分阻止这种作用，表明B7-H1信号转导能促进T细胞的凋亡。我们的结果表明，HBx抗原可以启动B7-H1在肝癌细胞中的表达，从而诱导T细胞凋亡，最终可能促进肝细胞癌的发生。
The cross-talk between the hepatitis B virus X protein (HBx) and B7-H1 in hepatocarcinoma (HCC) is unclear. This study analyzed the potential relationships between HBx and B7-H1 in hepatocarcinogenesis. One of human HCC cell lines, HepG2 cells, was transfected to stably express HBx protein (HBx+-HepG2). The transcription of B7-H1 mRNA was increased significantly in these cells compared to cells transfected with control vector (HBx--HepG2), as confirmed by a comparative genome-wide microarray analysis (Capitalbio) and real time quantitative PCR (qPCR). Flow cytometry and western-blot further demonstrated that B7-H1 protein synthesis was enhanced in HBx+-HepG2 cells. Site-directed mutagenesis of promoter constructs revealed that the transcription factor (NF)-κB binding site between 128 and 137 bp upstream of B7-H1 gene transcriptional start site is primarily responsible for HBx‐mediated B7-H1 expression. Co-culture experiments with HBx+-HepG2/T cells showed that the number of apoptotic T cells increased profoundly, and this effect could be partially prevented when a neutralizing mAb against B7-H1 was added to the culture, demonstrating that B7-H1 signaling can promote T cell apoptosis. Our results suggest that the expression of B7-H1 in hepatocarcimona cells can be initiated by HBx antigen, thus inducing T cell apoptosis and finally potentially facilitates the genesis of HCC.
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影响因子：
11.2
作者：
F. Hirano;K. Kaneko;H. Tamura;Haidong Dong;Shengdian Wang;Masao Ichikawa;C. Rietz;D. Flies
通讯作者：
F. Hirano;K. Kaneko;H. Tamura;Haidong Dong;Shengdian Wang;Masao Ichikawa;C. Rietz;D. Flies
影响因子：
25.7
作者：
Muehlbauer, Marcus;Fleck, Martin;Hellerbrand, Claus
通讯作者：
Hellerbrand, Claus
影响因子：
11.2
作者：
Blank, C;Brown, I;Gajewski, TF
通讯作者：
Gajewski, TF
DOI：
10.1172/jci118427
发表时间：
1996-01
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Y. Yoo;H. Ueda;K. Park;K. Flanders;Y. I. Lee;G. Jay;Seong-Jin Kim
通讯作者：
Y. Yoo;H. Ueda;K. Park;K. Flanders;Y. I. Lee;G. Jay;Seong-Jin Kim
PD-L1 的过度表达与人类肝细胞癌的肿瘤侵袭性和术后复发显着相关。
影响因子：
11.5
作者：
Gao, Qiang;Wang, Xiao-Ying;Fan, Jia
通讯作者：
Fan, Jia