Molecular investigation on the hepatic caicinogenesis-resistant model animals

肝脏抗癌模型动物的分子研究

基本信息

批准号：
11557090
负责人：
MIURA Naoyuki
金额：
$ 4.03万
依托单位：
Hamamatsu University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

项目摘要

The Rb gene was isolated as the causative gen of retinoblastoma. The Rb protein has an anti-proliferative action and has been known to be lost in many tumors. We made the transgenic mice in the liver of which the Rb protein was overexpressed in order to investigate the in vivo roles of Rb protein. Line A has 11 copies/haploid of the transgenes and line B has 4 copies/haploid. Consistently, a large amount of Rb protein was detected in the liver of line A transgenic mice and a small amount of it was detected in that of line B transgenic mice. The two lines of mice developed normally and the livers were normal in size and histology.We investigated whether the Rb transgenic mice showed resistance to chemical carcinogenesis. We inject diethylnitrosamine into the peritoneal cavity at the ages of 4 and 6 weeks and treated phenobarbital in drinking water for 35 weeks. After the experiment, the mice were sacrificed to make histological sections for counting the numbers of hepatocellular carcinoma and hepatic nodule. In control mice, a large number of nodules and several hepatocellular carcinoma were developed In contrast, the number of nodules was greatly reduced and no hepatocellular carcinomas were detected in both lines of Rb transgenic mice. The anti-carcinogenic effect of Rb gene was demonstrated in the experiments using the 4 week old mice and the 6 week old mice. These results indicate that the HNF1-Rb gene unit might be useful for the preventive medicine in the near future.

Rb基因被分离为视网膜细胞瘤的致病基因。 RB蛋白具有抗增殖作用，已知在许多肿瘤中丧失。我们使Rb蛋白过表达的肝脏中的转基因小鼠为了研究Rb蛋白的体内作用。线A具有11份/单倍体的转基因，B线B具有4个副本/单倍体。一致地，在A的A型转基因小鼠的肝脏中检测到大量的RB蛋白，并在B转基因小鼠中检测到少量RB蛋白。两条小鼠正常发育，肝脏的大小和组织学正常。我们研究了RB转基因小鼠是否表现出对化学癌变的抗性。我们在4和6周的年龄在腹膜腔中注入二乙基硝基胺，并在饮用水中处理苯巴比妥35周。实验后，牺牲小鼠以进行组织学切片，以计算肝细胞癌和肝结节的数量。在对照小鼠中，大量结节和几个肝细胞癌相反，在RB转基因小鼠的两条线中都没有检测到结节的数量，并且未检测到肝细胞癌的数量。在实验中使用了4周大的小鼠和6周大的小鼠，在实验中证明了RB基因的抗癌作用。这些结果表明，HNF1-RB基因单元在不久的将来可能对预防医学有用。