| Project/Area Number |
08264108
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Research Institution | Cancer Institute Carcinogenesis |
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Principal Investigator |
HINO Okio Cancer Institute, Dept.of Experimental Pathology, Chief, 癌研究所・実験病理部, 部長 (90127910)
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| Co-Investigator(Kenkyū-buntansha) |
KOBAYASHI Toshiyuki Cancer Institute, Dept.of Experimental Pathology, Research Associate, 癌研究所・実験病理部, 研究員 (40260070)
小西 陽一 奈良県立医科大学, 教授 (00075061)
松山 睦司 藤田保健衛生大学, 医学部, 教授 (80073112)
白井 智之 名古屋市立大学, 医学部, 教授 (60080066)
榎本 克彦 秋田大学, 医学部, 教授 (20151988)
芹川 忠夫 京都大学, 医学部, 教授 (30025655)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥107,000,000 (Direct Cost: ¥107,000,000)
Fiscal Year 1999: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1998: ¥33,000,000 (Direct Cost: ¥33,000,000)
Fiscal Year 1997: ¥33,000,000 (Direct Cost: ¥33,000,000)
Fiscal Year 1996: ¥36,000,000 (Direct Cost: ¥36,000,000)
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| Keywords | Eker rat / Animal model / Hereditary renal carcinoma / Tsc2 gene / Tuberous sclerosis / Tumor suppressor gene / Multistage carcinogenesis / 遺伝性癌 / 癌感受性遺伝子 / LECラット / BUM / Mnaラット / ラットゲノム / BUF / ラット発癌 / 腎癌 / 肝癌 / 前立腺癌 / 胸腺腫 / wilms腫瘍 / Canier Genetics |
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| Research Abstract |
Cancer is a heritable disorder of somatic cells. Enviroment and heredity both operate in the origin of human cancer. The Tsc2gene mutant (Eker) rat model of hereditary renal carcinoma (RC) is an example of mendelian dominantly inherited predisposition to a specific cancer in an experimantal animal. We used theses unique aniaml models for the study of preblems in carcinogenesis (e.g., tissue/cell-type specific tumorigenesis, multistage carcinogenesis and species-specific difference in tumorigenesis). (1) animal models homologous to human genetic conditions and helpfil toward understanding non-hereditary conditions. (2) opportunity to study earlist lesions. (3) can use strain differences in phenotype to find genetic modifiers of phenotype and possible use for prevention and tratment.
The phenotype in human differs from that in the Eker rat, except for the occurrence of RCs (in human, angiomyolipomas are more common), although we found subepedymal and subcortical hamartomas in the Eker rats. Thus, the same gene shows diverse phenotype between species, although we do not have any good explanation for this difference. To elicit insights into species-specific cumorigenesis caused by Tsc2 gene inactivation, we generated a Tsc2 knock out mice. Mice homozygous for Tsc2 mutation developed RCs but no angiomyolipoma, with a complete penetrance as seen in the Eker rat.
Thus, TSC genes mutants continues to be a valuable experimental models for understanding the mechanisms of disease, and the development of the therapeutic treatments which can be translated into human patients as well as how enviromental factors interact with cancer susceptibility genes.
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