HBx induced AFP receptor expressed to activate PI3K/AKT signal to promote expression of Src in liver cells and hepatoma cells.
HBx induced AFP receptor expressed to activate PI3K/AKT signal to promote expression of Src in liver cells and hepatoma cells.
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HBx诱导AFP受体表达激活PI3K/AKT信号促进肝细胞和肝癌细胞中Src的表达
DOI：
10.1186/s12885-015-1384-9
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发表时间：
2015-05-06
期刊：
影响因子：
3.8
通讯作者：
Li M
中科院分区：
文献类型：
--
作者：
Zhu M;Guo J;Li W;Xia H;Lu Y;Dong X;Chen Y;Xie X;Fu S;Li M
背景B型肝炎病毒（Hepatitis B virus，HBV）-X蛋白（HBx）是甲胎蛋白（alpha-fetoprotein，AFP）和甲胎蛋白受体（AFP receptor，AFPR）等多种细胞基因的反式激活因子，参与HBV相关肿瘤的发生发展。AFP/AFPR的表达与原发性肝细胞癌（HCC）的发生有关。方法选取71例临床患者肝组织标本、正常人肝细胞L-02和肝癌细胞系PLC/PRF/5，分析HBx对AFP、AFPR和Src表达的影响。免疫组化染色和Western blotting检测目的蛋白的表达;构建HBx表达载体，转染L-02细胞，激光共聚焦显微镜观察AFP、AFPR和Src在正常肝细胞和肝癌细胞中的表达和定位，用软琼脂集落形成实验观察细胞集落形成情况。AFP和AFPR; HBx可上调L-02细胞和正常肝脏标本中AFPR和AFP的表达; AFPR信号能够刺激Src的表达。结论在正常肝细胞和肝癌细胞中，HBx可诱导AFP和AFPR的表达，从而促进Src的表达，AFP和AFPR可能在HBV相关的肝癌发生中起关键作用;以AFPR为靶点治疗肝癌是一种有效的治疗策略。
BackgroundHepatitis B virus (HBV)-X protein(HBx) is a transactivator of host several cellular genes including alpha-fetoprotein(AFP) and AFP receptor(AFPR) which contributes to HBV-associated tumor development. The expression of AFP/AFPR are correlated with hepatocellular carcinoma(HCC)-initial cells. But the role of AFP and AFPR in promoting occurrence of HBV-related HCC were still unclear.MethodsA total of 71 clinical patients’ liver specimens, normal human liver cells L-02 and HCC cell lines, PLC/PRF/5 were selected for analyzing the effects of HBx on expression of AFP, AFPR and Src. The expression of goal proteins were detected by Immunohistochemical stained and Western blotting; HBx-expressed vectors were constructed and transfected into L-02 cells, laser confocal microscopy was applied to observe expression and location of AFP, AFPR and Src in the normal liver cells and HCC cells, soft agar colony formation assay was used to observe colonies formed of the cells.ResultsWe confirmed HBx gives preference to promote the expression of AFP and AFPR; HBx priors to up-regulate the expression of AFPR and AFP in L-02 cells and in normal liver specimens; AFPR signal been able to stimulate Src expression. The results also indicated that phosphatidylinositol 3-kinase(PI3K) inhibitors Ly294002 and GDC0941 effectively suppress AFPR mediated up-regulation expression of Src in AFPR positive HCC lines.ConclusionsHBx priors to drive the expression of AFP and AFPR to promote expression of Src in normal liver cells and hepatoma cells; AFP and AFPR maybe play pivotal role in HBV-related hepatocarcinogenesis; Targeting AFPR is an available therapeutic strategy of HCC.
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影响因子：
4.8
作者：
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