1991 Fiscal Year Final Research Report Summary
TRANSGENIC MOUSE MODEL FOR GASTRIC AND HEPATOCELLULAR CARCINOMA
| Project/Area Number |
02454228
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Gastroenterology
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| Research Institution | UNIVERSITY OF TOKYO |
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Principal Investigator |
IINO Shiro UNIV.OF TOKYO,DEPT.OF INTERN.MED., LECTURER., 医学部(病), 講師 (30010309)
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| Co-Investigator(Kenkyū-buntansha) |
YOTSUYANAGI Hiroshi UNIV.OF TOKYO,DEPT.OF INTERN.MED., MD, 医学部(病), 医員 (30251234)
KOIKE Kazuhiko UNIV.OF TOKYO,DEPT.OF INTERN.MED., ASSIST.PROF., 医学部(病), 助手 (90234658)
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| Project Period (FY) |
1990 – 1991
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| Keywords | gastric carcinoma / hepatocellular carcinoma / transgenic mice / adenovirus E1 gene / hepatitis B virus / HBx gene |
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| Research Abstract |
To elucidate the pathogenesis of gastric cancer and hepatocellular carcinoma in human, we generated transgenic mice into which adenovirus early region 1 (E1) and hepatitis B virus HBx gene, respectively. In adenovirus E1 mice, gastric hyperplasia, adenoma and finally adenocarcnima developed in the conjunction between forestomach and follicular epithelium. High-level expression of both E1A and E1B genes were observed in these neoplastic lesions. In contrast, transgenic mouse lineages which had onlt E1 gene or E1B gene did not show gastric cancer espite the expression of each gene. These results indicate that co-operation of more than 2 oncogenes are necessary for carcinogenesis in vivo as well as previously shown in cultred cells.
To make a model of hepatocarcinogenesis, we produed transgenic mice which had hepatitis B virus HBx gene under its own regulatory elelments. In this transgenic mouse line, along with the expression of HBx gene from birth progressive histologic lesion appeared beginning from proliferative foci and benign adenoma, and finally developing to malignant hepatocellular carcinoma. This result demonstrates a direct relationship between hepatitis B virus and hepatocellualr carcnioma for the first time.
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