signal Transduction pathways in regenerating liver and the role of HBV X gene

乙型肝炎病毒(乙肝病毒)和丙型肝炎病毒(丙型肝炎病毒)可直接或间接引起参与细胞增殖调控的信号转导途径的改变。肝细胞自身的反复再生可能会引起调节机制的改变。为了探讨信号转导途径改变的可能机制，我们检测了端粒菌素对整合了HBVDNA的PLC/PRF/5肝癌细胞的影响。端粒菌素是一种肿瘤促进剂，其作用可能是通过蛋白激酶-EC介导的，它抑制了细胞的增殖，并显著改变了细胞的形态。柱层析显示C-激酶活性存在三个峰。其中两个基因表达下调，而第三个基因的表达没有因长时间的终末杀菌素而下调。在未洗脱蛋白激酶C的柱组分中检测到第三个峰的C-激酶活性，表明该蛋白激酶的分子结构与通常的蛋白激酶C的分子结构不同。这些数据表明，这些肝癌细胞中存在类似C-激酶的蛋白激酶。由于已知HBVX基因可以促进其他基因的表达，因此可以推测X基因的表达可能导致这种类似C-激酶的蛋白的产生。需要进一步的研究来证明这一假设。

Hepatitis B virus(HBV)and hepatitis C virus(HCV)may cause alterations of signal transduction pathways involved in the regulation of cell proliferation either directly or indirectly. Repeated regeneration of hepatocyte itself may cause alterations of the regulatory mechanism. To investigate the possible mechanism of the alterations of signal transduction pathways we examined the effects of teleocidin on PLC/PRF/5 hepatoma cells which had integrated form of HBV DNA.Teleocidin, a tumor promoter whose actions are believed to be mediated by protein kinas-e C, acted inhibitory on cell proliferation and altered morphological appearance remarkably. Column chromatography disclosed the presence of three peaks of C-kinase activity. Two of which were down regulated while the third one is not down regulated by prolonged incubation with teleocidin. The C-kinase activity of the third peak was detected in the column fractions into which usual protein kinase C was not eluted, indicating that the molecular structure of the protein kinase was different from those of usual protein kinase C. Those data suggest that C-kinase like protein kinase exists in these hepatoma cells.Since HBV X gene is known to enhance the expression of other genes, it can be speculated that the expression of X gene may cause the production of this C-kinase like protein. Further investigation is necessary to prove this supposition.