1998 Fiscal Year Final Research Report Summary
Pathogenesis of Human Tuberous Sclerosis
| Project/Area Number |
09470068
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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 | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Cancer Institute |
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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) |
ORIMOTO Kenji Cancer Institute, Dept.of Experimental Pathology, Associate, 癌研究所・実験病理部, 研究員 (50290953)
KOBAYASHI Toshiyuki Cancer Institute, Dept.of Experimental Pathology, Associate, 癌研究所・実験病理部, 研究員 (40260070)
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| Project Period (FY) |
1997 – 1998
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| Keywords | Human tuberous sclerosis / TSC2 gene / TSCI gene / Tumor suppressor gene / Anima model |
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| Research Abstract |
Human tuberous sclerosis is an autosomal dominant multisystem disorder characterized by phacomatosis with manifestations that include mental retardation, seizures and neoplastic lesions.Although their nature and pathogenesis had been obscure for more than a century since their fist description in the medical literature, recent advancements in molecular biology and genetics has enabled identification of the responsible gene or genes of these diseases and allowed insight into their pathogenesis and especially their neoplastic process.Because nothing is known about the molecular mechanism of human tuberous sclerosis, the Tsc2 gene mutant (Eker) rat has great potential for elucidating the TSC2 gene role in renal carcinogenesis, as well as studying species-specific differences in tumorigenesis and/or cell-type specific carcinogenesis. Moreover, there are effects of genetic background on renal carcinogenesis in the Eker rat model.These data indicate there is a modifier gene(s) that suppresses the growth of tumors.The identification of such a modifier gene(s) might help to understand diverse phenotypes in humans.
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[Publications] Kobayashi, T., Urakami, S., Hirayama, Y., Yamamoto, T., Nishizaw, M., Takahara, T.and Hino O.: "Intragenic Tsc2 somatic mutations as Knudson's second hit in spontaneous and chemically induced renal carcinomas in the Eker rat model" Jpn.J.Cancer Res. 88. 254-261 (1997)
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「研究成果報告書概要(欧文)」より
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[Publications] Kobayashi, T., Mitani, H., Takahashi, R., Hirabayashi, M., Ueda, M., Tamura, H.and Hino, O.: "Transgenic rescue from embryonic lethality and renal carcinogenesis in the Eker rat model by introduction of a wild-type Tsc2 gene." Proc.Natl.Acad.Sci.USA.94. 3990-3993 (1997)
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[Publications] Kobayashi, T., Urakami, S., Cheadle, J.P., Aspinwall, R., Harris, P., Sampson, J.R.and Hino, O.: "Identification of a leader exon and a core promoter for the rat tuberous sclerosis 2 (Tsc2) gene and structural comparison with the human homologue" Mammalian Genome. 8. 554-558 (1997)
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[Publications] Urakami, S., Tsuchiya, H., Orimoto, K., Kobayashi, T., Igawa, M.and Hino, O.: "Overexpression of members of the AP-1 transcriptional factor family from an early stage of renal carcinogenesis and inhibition of cell growth by AP-1 gene antisense oligonucleotides in the Tsc2 gene mutant (Eker) rat model." Biochem.Biophys.Res.Commun.241. 24-30 (1997)
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[Publications] Toyokuni, S., Okada, K., Kondo, S., Nishioka, H., Tanaka, T., Nishiyama, Y., Hino, O.and Hiai, H.: "Development of high-grade renal cell carcinomas in rats idenpendently of somatic mutations in the Tsc2 and VHL tumor suppressor genes." Jpn. J.Cancer Res.89. 814-820 (1998)
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[Publications] Fukuda, T., Hirayama, Y., Mitani, H., Maeda, H., Konishi, Y.and Hino, O .: "Generation of metastatic variants of Eker renal carcinoma cell lines for experimental investigation of renal cancer metastasis." Jpn. J.Cancer. 89. 1104-1108 (1998)
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[Publications] Hino, O., Fnkuda, 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 Progress in Experimental Tumor Research Vol.35. (Eds.Hiai, H.and Hino, O.), Karger(in press),
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[Publications] Fnkuda, 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(in press.),
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[Publications] Hino, O., Satake, N., Kobayashi, T.and Kajino, K.: Carcinogenesis in tuberous sclerosis. Gann Monograph on Cancer Research In Phacomatosis in Japan-Epidemiology, clinical picture and molecular biology. (Eds.Niimura, M., Ohtuka, F.and Hino., O, ], Japan Scientific Societies Press, Tokyo(in press.),
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