2001 Fiscal Year Final Research Report Summary
Molecular investigation on the hepatic caicinogenesis-resistant model animals
| Project/Area Number |
11557090
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Digestive surgery
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| Research Institution | Hamamatsu University School of Medicine |
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Principal Investigator |
MIURA Naoyuki Hamamatsu University, School of Medicine, Professor, 医学部, 教授 (40165965)
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| Co-Investigator(Kenkyū-buntansha) |
KAWARADA Yoshihiko Akita University, School of Medicine, Assistant Professor, 医学部, 講師 (10091802)
TERADA Kunihiko Akita University, School of Medicine, Associate Professor, 医学部, 助教授 (60197796)
UEZATO Tadayoshi Hamamatsu University, School of Medicine, Associate Professor, 医学部, 助教授 (40115465)
SATO Eiji Hamamatsu University, School of Medicine, Res. Associate, 医学部, 助手 (70118751)
TAKEUCHI Takashi Mitsubishi Kasei Institute of Life Sciences, Chief Investigator, 先端研究部門, 主任研究員
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| Project Period (FY) |
1999 – 2001
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| Keywords | Rb protein / Transgenic mice / Hepatocellular carcinome / Nodule / HNF1 / Chemical carcinogenesis / Preventive medicine |
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| Research Abstract |
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.
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