Abstract：
Chronic HBV infection is a major cause of hepatocellular carcinoma (HCC) worldwide. The phenotypes of HCC are diverse, in part, due to mutations in distinct oncogenes and/or tumor suppressor genes. These genetic drivers of HCC development have generally been considered as major mediators of tumor heterogeneity. Using the liver-specific Pten-null HBV transgenic mouse model of chronic viral infection, a critical role for liver lobule zone-specific gene expression patterns in determining HCC phenotype and β-catenin-dependent HBV biosynthesis is demonstrated. These observations suggest that the position of the hepatocyte within the liver lobule, and hence its intrinsic gene expression pattern at the time of cellular transformation, make critical contributions to the properties of the resulting liver tumor. These results may explain why therapies targeting pathways modulated by specific identified tumor driver genes display variable treatment efficacy.
摘要：
慢性HBV感染是全球肝细胞癌（HCC）的主要原因。肝癌的表型是多样的，在某种程度上,由于不同的癌基因和/或肿瘤抑制基因突变。HCC发展的这些遗传驱动因素通常被认为是肿瘤异质性的主要介质。使用慢性病毒感染的肝脏特异性Pten-nullHBV转基因小鼠模型，证明了肝小叶区特异性基因表达模式在确定HCC表型和β-catenin依赖性HBV生物合成中的关键作用。这些观察结果表明，肝细胞在肝小叶内的位置，因此它在细胞转化时的内在基因表达模式，对所产生的肝肿瘤的性质做出关键贡献。这些结果可以解释为什么靶向由特定鉴定的肿瘤驱动基因调节的途径的疗法显示可变的治疗功效。
