MOLECULAR PATHOGENESIS OF HEPATOCELLULAR-CARCINOMA IN HEPATITIS-B VIRUS TRANSGENIC MICE
MOLECULAR PATHOGENESIS OF HEPATOCELLULAR-CARCINOMA IN HEPATITIS-B VIRUS TRANSGENIC MICE
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DOI：
10.1016/0092-8674(89)90770-8
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发表时间：
1989-12-22
期刊：
影响因子：
64.5
通讯作者：
PALMITER, RD
中科院分区：
文献类型：
--
作者：
CHISARI, FV;KLOPCHIN, K;PALMITER, RD
过量产生B型肝炎病毒大包膜多肽并在肝细胞内积累毒性量的B型肝炎表面抗原（HBsAg）的转基因小鼠发生严重的、长期的肝细胞损伤，其在肝脏内启动程序性应答，其特征在于炎症、再生性增生、转录失调和非整倍性。这种反应不可避免地发展为瘤形成。该模型中肝细胞癌的发生率与肝细胞损伤的频率、严重程度和发病年龄相对应，而肝细胞损伤本身与HBsAg的肝内浓度相对应，并受遗传背景和性别的影响。因此，在该模型中，单个结构病毒基因的不适当表达足以引起恶性转化。这些结果表明，严重的，长期的细胞损伤诱导癌前增殖反应，促进继发性遗传事件，程序细胞无限制的增长。
Transgenic mice that overproduce the hepatitis B virus large envelope polypeptide and accumulate toxic quantities of hepatities of hepatitis B surface antigen (HBsAg) within the hepatocyte develop severe, prolonged hepatocellular injury that initiates a programmed response within the liver, characterized by inflammation, regenerative hyperplasia, transcriptional deregulation, and aneuploidy. This response inexorably progresses to neoplasia. The incidence of hepatocellular carcinoma in this model corresponds to the frequency, severity, and age of onset of liver cell injury, which itself corresponds to the intrahepatic concentration of HBsAg and is influenced by genetic background and sex. Thus, the inappropriate expression of a single structural viral gene is sufficient to cause malignant transformation in this model. These results suggest that severe, prolonged cellular injury induces a preneoplastic proliferative response that fosters secondary genetic events that program the cell for unrestrained growth.