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

在慢性乙型肝炎患者中，X蛋白表达于肝细胞胞浆。X蛋白阳性肝细胞与HBcAg阳性肝细胞的分布呈正相关。此外，X蛋白阳性患者的血清HBVDNA水平明显高于X蛋白阴性患者，提示肝组织中表达的X蛋白可能促进了体内HBVDNA的复制。我们检测了3例B型肝细胞癌患者，X蛋白在3例患者的癌区均不表达，但在2例患者的非癌区有表达。提示X蛋白与肝细胞癌变的早期阶段有一定关系。然而，X蛋白不太可能发挥维持肝细胞癌的功能。此外，在慢性乙型肝炎和肝硬变患者中，c-myc的表达频率在X蛋白…患者中显著升高在没有X蛋白的情况下，情况会更糟。但X蛋白的分布与c-myc的分布不同。因此，目前尚不清楚在B型慢性肝病患者中，c-myc和c-Ha-ras等癌基因的表达是由X蛋白直接诱导的，还是由炎症间接诱导的。从这个角度来看，有必要进行进一步的研究。此外，我们利用整合了HBVDNA的HUH6细胞系发展而来的HB611细胞株，研究了乙肝病毒复制与乙肝病毒感染的肝细胞表达人类白细胞抗原的能力之间的关系。在该细胞系中，X蛋白定位于核周细胞质中。用无环鸟苷抑制HB611的复制可增加HB611表面HLAI类抗原的表达，提示HB611的复制可能抑制了HLAI类抗原的表达。人类白细胞抗原表达降低可能会削弱免疫监视系统识别抗原的能力，并被认为与肿瘤的发生有一定关系。进一步的研究还有待于总结。较少

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