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

乙型肝炎病毒（HBV）和丙型肝炎病毒（HCV）可能直接或间接引起参与细胞增殖调节的信号转导通路的改变。肝细胞自身的反复再生可能引起调节机制的改变。为了探讨信号转导通路改变的可能机制，我们研究了远杀素对具有HBV DNA整合形式的PLC/PRF/5肝癌细胞的影响。远杀丝蛋白是一种肿瘤启动子，其作用被认为是由蛋白激酶-e - C介导的，对细胞增殖和形态外观有明显的抑制作用。柱层析显示存在三个c -激酶活性峰。其中两个是下调的，而第三个则没有下调通过与远杀虫素长时间孵育。在常规蛋白激酶C未洗脱的柱段中检测到第三峰的C激酶活性，表明该蛋白激酶的分子结构与常规蛋白激酶C不同。这些数据表明在这些肝癌细胞中存在类似C激酶的蛋白激酶。由于已知HBV X基因可增强其他基因的表达，因此可以推测，X基因的表达可能导致这种c激酶样蛋白的产生。需要进一步的调查来证明这一假设。

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.