ROLE OF THE HEPATITIS B VIRUS IN INDUCING MALIGNANCIES I

这项提案的长期目标是定义HBx基因的作用 人乙肝病毒在小鼠肝细胞癌诱导中的作用 转基因小鼠，并将该转基因小鼠模型应用于 对人类多阶段癌变分子机制的认识 人类。 该项目有四个相互关联的具体目标：[1]定义 乙型肝炎病毒X基因(命名为HBx基因)在通过以下途径诱导发病中的作用 将该基因在其自身转录控制信号下导入 小鼠的生殖系；[2]以加速疾病的表型，这可能是 通过将HBx基因置于小鼠的控制区下而诱导 白蛋白基因，并利用该嵌合构建物获得转基因小鼠 将表达高水平的HBx基因产物；[3]以确定 协同因素的重要性，这些因素可能会在诱导或 增强转基因小鼠的肝病表现；[4] 确定哪些细胞基因和细胞基因产物是 在HBx转基因小鼠的肝脏中特异性激活并 阐明它们在发病过程中的作用。 预计这种转基因动物的出现将 BU不仅有助于我们理解乙肝病毒引起的疾病，还可能 有助于阐明致癌的分子机制。

The long term goals of this proposal are to define the role of the HBx gene of human hepatitis B virus (HBV) in inducing hepatocellular carcinoma in transgenic mice, and to apply this transgenic mouse model toward the understanding of the molecular mechanisms for multistage carcinogenesis in humans. This project has four specific bu interrelated aims: [1] to define the role of the HBV X gene (designated HBx gene) in inducing pathogenesis by introducing this gene under its own transcriptional control signals into the germline of mice; [2] to accelerate the disease phenotype that may be induced by the HBx gene by placing it under the control region of the mouse albumin gene and using this chimeric construct to derive transgenic mice which will express high levels of the HBx gene product; [3] to determine the importance of co-factors which may play a role in either inducing or enhancing the manifestation of liver disease in the transgenic mice; [4] to identify the cellular genes and cellular gene products which are specifically activated in the liver of the HBx transgenic mice and to delineate their roles in the process of pathogenesis. It is anticipated that the availability of such transgenic animals would not only facilitate our understanding of HBV-induced disorders, bu may also help elucidate the molecular mechanisms of carcinogenesis.