Study on the effects of hepatites B virus X-gene expression on hepato-carcinogenesis.

慢性乙型肝炎患者肝细胞细胞质中表达X蛋白。X蛋白阳性肝细胞分布与hbcag阳性肝细胞分布相关。此外，X蛋白阳性患者血清HBV DNA水平显著高于X蛋白阴性患者，提示肝脏组织中表达的X蛋白可能会增强HBV在体内的复制。当我们检查了3例B型肝细胞癌（HCC）患者时，X蛋白在3例患者的癌区均不表达，但在3例患者中的2例非癌区表达。这些发现提示X蛋白与肝癌早期发生有一定关系。然而，X蛋白不太可能起维持HCC的作用。此外，在B型慢性肝炎和肝硬化患者中，有X蛋白的患者c-myc的表达频率明显高于无X蛋白的患者。但X蛋白的分布与c-myc不同。因此，目前尚不清楚在B型慢性肝病患者中，c-myc、c-Ha-ras等癌基因的表达是由X蛋白直接诱导的，还是炎症间接诱导的。从这一点来看，进一步的研究是必要的。此外，我们利用整合HBV- dna从HUH6细胞系发展而来的HB611细胞系，研究了HBV复制与HBV感染肝细胞表达HLA抗原的能力之间的关系。该细胞系核周细胞质中可见X蛋白。用阿昔环霉素预处理该HB611抑制HBV复制后，HB611上HLA I类抗原的表达增加，提示HBV复制可能抑制HLA抗原的表达。HLA抗原表达降低可能损害免疫监视系统对抗原的识别能力，被认为与恶性肿瘤有一定关系。有必要进一步研究得出结论。少

In patients with type B chronic hepatitis, X protein was expressed in cytoplasm of hepatocyte. The distribution of X protein-positive hepatocytes was correlated with that of HBcAg-positive ones. Furthermore, serum HBV DNA levels of X protein-positive patients were significantly higher than those of X protein-negative ones, suggesting that X protein which was expressed in liver tissue might enhance the replication of HBV in vivo. When we examined three cases of patients with type B hepatocellular carcinoma (HCC), X protein was not expressed in cancerous region of all three patients, but was expressed in non-cancerous region of two of three patients. These findings suggested that X protein had some relations to a early stage of hapato-carcinogenesis. However, it was unlikely that X protein might function to maintain HCC. Furthermore, in patients with type B chronic hepatitis and liver cirrhosis, the frequency of the expression of c-myc was significantly higher in patients with X protein … More than that without X protein. However, the distribution of X protein was different from that of c-myc. Therfore, at present, it is unclear whether, in patients with type B chronic liver disease, the expression of oncogenes such as c-myc and c-Ha-ras were directly induced by X protein or indirectly induced as a result of inflammation. From this point of view, further study is necessary.Moreover, we examined a relationship between HBV replication and the ability of HBV-infected hepatocytes to express HLA antigen, using HB611 cell line which was developed from HUH6 cell line by integrating HBV-DNA. In this cell line, X protein was observed in peri-nuclear cytoplasm. Pretreatment of this HB611 with acyclocir to inhibit HBV replication increased the expression of HLA class I antigen on HB611, suggesting that HBV replication might suppress the expression of HLA antigen. Decreased expression of HLA antigen might impair the ability of immunosurveillance system to recognize antigens and is considered to have some relations to malignancy. Further study is necessary to be concluded. Less