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2000 Fiscal Year Final Research Report Summary

Multistage carcinogenesis in TSC gene mutant models

Research Project

Project/Area Number 08264108
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Research InstitutionCancer Institute Carcinogenesis

Principal Investigator

HINO Okio  Cancer Institute, Dept.of Experimental Pathology, Chief, 癌研究所・実験病理部, 部長 (90127910)

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)
Project Period (FY) 1999 – 2000
KeywordsEker rat / Animal model / Hereditary renal carcinoma / Tsc2 gene / Tuberous sclerosis / Tumor suppressor gene / Multistage carcinogenesis
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.

  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Satake,N.: "Isolation and characterization of a rat homologue of the human tuberous sclerosis 1 gene (TSC1) and analysis..."Cancer Res. 59. 849-855 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kobayashi,T.: "Renal carcinogenesis, hepatic hemangiomatosis and embryonic lathality caused by a germiline TSC2..."Cancer Res.. 59. 1206-1211 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fukuda,T.: "Distribution of TSC2 protein in various normal rat tissues and renal tumors of TSC2 mutant (Eker) rat..."Virchows.Archiv. 434. 341-350 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fukuda,T: "Cloning of differentially expressed genes in highly and low metastatic rat osteosaroomas by a modified"Biochem.Biophys.Res.Commun. 261. 35-40 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamashita,Y.: "Analysis of the entire TSC1 and TSC2 gene for germline mutations in Japanese cases of Tuberous"Am.J.Med.Genet. 90. 123-126 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Mizuguchi,M,: "Novel cerebral lesions in the Eker rat model of tuberous sclerosis, Cortical tuber and ansplastic..."J.Neuropathol.Exp.Neurol. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hino,O.: "Animal Models of Cancer Predisposition syndromes"Karger, Basel. 175 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hino,O: "Phacomatosis. in Japan"Japan Screntific Societies. Press. 229 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Satake, N., Kobayashi, T., Kobayashi, E,, Izumi, K.and Hino, O.: "Isolation and characterization of a rat homologue of the human tuberous sclerosis 1 gene (TSC 1) and analysis of its mutations in rat renal carcinomas."Cancer Res.. 59. 849-855 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kobayashi, T., Minow, O., Kuno, J., Mitani, H.Hino O.and Noda T: "Renal carcinogenesis, hepatic hemangiomatosis and embryonic lethality caused by a germline Tsc 2 mutation in mice."Cancer Res.. 59. 1206-1211 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hino, O., Fukuda, T., Satake, N., Kobayashi, T., Honda, S., Orimoto, K., Yamashita, Y.and Kikuchi, Y.: "TSC2 gene mutant (Eker) rat model of a mendelian dominantly inherited cancer."Prog.Exp.Tumor Res.(Eds.Hiai, H.and Hino, O,), Karger, Basel. 35. 95-108 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fukuda, T., Kobayashi, T., Yasui, H., Tsutsumi, M., Konishi, Y.and Hino, O.: "Distribution of Tsc2 protein in various normal rat tissues and renal tumors of Tsc2 mutant (Eker) rat detected by immunohistochemistry"Virchows Archiv. 434. 341-350 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kajino, K.and Hino, O.: "TSC 1 and TSC 2 genes mutations in Human Kidney tumors. "Kidney Cancer" (Recent Results of Basic and Clinical Research) In Contibution to Nephrology (Ed.Hino, O.)"Karger, Basel. 128. 45-50 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fukuda, T., Kido, A., Kajino, K., Tsutsumi, M., Miyauchi, Y., Tsujiuchi, T., Konishi, Y.and Hino, O.: "Cloning of differentially expressed genes in highly and low metastatic rat osteosarcomas by a modified cDNA-AFLP method"Biochem.Biophys.Res.Commun.. 261. 35-40 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamashita, Y., Ono, J., Okada, S., Wataya-Kaneda, M., Yoshikawa, K., Nishizawa, M., Hirayama, Y., Kobayashi, E., Seyama, K.and Hino, O.: "Analysis of the entire TSC1 and TSC2 genes for germline mutations in Japanese cases of tuberous sclerosis : Reports of ten mutations"Am.J.Med.Genet. 90. 123-126 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mizuguch, M., Takashima, S., Yamanouch, H., Nakazato, Y., Mitani, H.and Hino, O.: "Novel cerebral lesions in the Eker rat model of tuberous sclerosis, Cortical tuber and anaplastic ganglioglioma"J.Neuropathol.Exp.Neurol.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hino, O., Satake, N., Kobayashi, T.and Kajino, K.: "Carcinogenesis in tuberous sclerosis. Gann Monograph on Cancer Reserach No.46 : (Eds.Ohtuka, F., Hino, O.and Niimura, M.)"Japan Scientific Societies Press, Tokyo. 101-111 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hino, O., Kobayashi, T., Orimoto, K., Urakami, S., Fukuda, T., Satake, N.and Yamashita, Y.: "Cancer genetics of the tuberous sclerosis (TSC2) gene mutant. Familal Cancer and Prevention (Eds.Utsunomiya, J., Mulvihill, J.J.and Weber, W.)"A Jone Wiley & Sons, Inc., New York. 475-480 (1999)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2002-03-26  

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