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Molecular investigation on the hepatic caicinogenesis-resistant model animals

Research Project

Project/Area Number 11557090
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Digestive surgery
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

MIURA Naoyuki  Hamamatsu University, School of Medicine, Professor, 医学部, 教授 (40165965)

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
吉田 進昭  東京大学, 医科学研究所, 教授 (10250341)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥6,300,000 (Direct Cost: ¥6,300,000)
Fiscal Year 2001: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2000: ¥3,900,000 (Direct Cost: ¥3,900,000)
KeywordsRb protein / Transgenic mice / Hepatocellular carcinome / Nodule / HNF1 / Chemical carcinogenesis / Preventive medicine / Rb蛋白 / 遺伝的背景 / フェノバルビタール
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.

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (35 results)

All Other

All Publications (35 results)

  • [Publications] Terada, K.: "Biliary excretion of copper in LEC rat after introduction of copper transporting P-type ATPase, ATP7B"FEBS Letter. 448. 53-56 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Komatsu, M.: "Copper-transporting P-type adenosine triphosphatase (ATP7B) is associated with cisplatin resistance"Cancer Res.. 60. 1312-1316 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Harada, M.: "Role of ATP7B in biliary copper excretion in a human hepatoma cell line and normal rat hepatocytes"Gastroenterology. 118. 921-928 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Roelofsen, H.: "Copper-induced apical trafficking of ATP7B in polarized hepatoma cells provides a mechanism for biliary copper excretion"Gastroenterology. 119. 782-793 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Wang, T.: "Inhibition effects of di(2-ethylhexyl)phthalate on mouse liver lysosomal Vacuolar H+-ATPase"J. Cell. Biochem.. 81. 295-303 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ichihara, T.: "Resistance to fulminant hepatitis and carcinogenesis conferred by overexpression of retinoblastoma protein in mouse liver"Hepatology. 33. 948-955 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 三浦直行: "Vascular Biologyナビゲーター"メディカルレビュー社. 373 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Terada, K. et al.: "Biliary excretion of copper in LEG rat after introduction of copper transporting P-type ATPase, ATP7B"FEES Letter. 448. 53-56 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Komatsu, M. et al.: "Copper-transporting P-type adenosine triphosphatase (ATP7B) is associated with cisplatin resistance"Cancer Res. 60. 1312-1316 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Harada, M. et al.: "Role of ATP7B in biliary copper excretion in a human hepatoma cell line and normal rat hepatocytes"Gastroenterology. 118. 921-928 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Roelofsen, H. et al.: "Copper-induced apical trafficking of ATP7B in polarized hepatoma cells provides a mechanism for biliary copper excretion"Gastroenterology. 119. 782-793 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Wang, T. et al.: "Inhibition effects of di(2-ethylhexyl)phthalate on mouse liver lysosomal Vacuolar H+-ATPase"J. Cell. Biochem.. 81. 295-303 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ichihara, T. et al.: "Resistance to fulminant hepatitis and carcinogenesis conferred by overexpression of retinoblastoma protein in mouse liver"Hepatology. 33. 948-955 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Miura, N.: "Vasculer Biology Navigator"Medical Review, Inc.. (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Wang, T.: "Inhibition effects of di(2-ethylhexyl)phthalate on mouse liver lysosomal Vacuolar H+-ATPase"J. Cell. Biochem.. 81. 295-303 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ichihara, T.: "Resistance to fulminant hepatitis and carcinogenesis conferred by overexpression of retinoblastoma protein in mouse liver"Hepatology. 33. 948-955 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nifuji, A.: "Bone morhogenetic protein regulation of forkhead/ winged helix transcription factor, Foxc2 (Mfh1) in a murine mesodermal cell line C1 and in skeletal precursor cells"J. Bone & Mineral Res.. 16. 1765-1771 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 三浦直行: "明らかになってきたフォークヘッド遺伝子の器官形成における役割"蛋白質核酸酵素. 46. 26-35 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 三浦直行: "22q11欠失症候群の遺伝子医学"遺伝子医学. 5. 204-211 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 三浦直行: "神経堤細胞の発生と分化"医学のあゆみ. 199. 1025-1030 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 三浦直行: "Vascular Biologyナビゲーター"メディカルレビュー社. 373 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Komatsu,M.: "Copper-transporting P-type adenosine triphosphatase(ATP7B)is associated with cisplatin resistance."Cancer Res.. 60. 1312-1316 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yang,X-L.: "MFH-1 is required for Bone-Mrphogenetic Protein-2-induced osteoblastic differentiation of C2C12 myoblasts."FEBS Letter. 470. 29-34 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Harada,M.: "Role of ATP7B in biliary copper excretion in a human hepatoma cell line and normal rat hepatocytes."Gastroenterology. 118. 921-928 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Eguchi,A.: "Identification and characterization of cell lines with defect in a post-adsorption stage of Sendai virus-mediated membrane fusion."J.Biol.Chem.. 275. 17549-17555 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Berg,D.: "Changes of copper transporting proteins and ceruloplasmin in the lentiform nuclei in primary adult-onset dystonia."Ann.Neurol.. 47. 827-830 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Roelofsen,H.: "Copper-induced apical trafficking of ATP7B in polarized hepatoma cells provides a mechanism for biliary copper excretion."Gastroenterology. 119. 782-793 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Miura,N.: "Etiology and morphogenesis of congenital heart disease : Twenty years of progress in genetics and developmental biology"Futura Publishing Co.. 389 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Terada,K.: "Biliary excretion of copper in LEC rat after introduction of copper transporting P-type ATPase, ATP7B"FEBS Letter. 448. 53-56 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Furumoto,T.: "Notochordo dependent expression of MFH-1 and Pax-1 cooperates to maintain the proliferation of sclerotome during vertebral columnn development"Dev.Biol.. 210. 15-29 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Masuda,Y.: "The fragment of complement 3a lacking the primary 9 amino acids induces promoting activity on mouse voluntary running"Tohoku J.Exp.Med.. 189. 21-27 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Komatsu,M.: "Cisplatin resistance conferred by copper transporting P-type ATPase cDNA(ATP7B)"Cancer Res.. (印刷中).

    • Related Report
      1999 Annual Research Report
  • [Publications] Yang,X-L..: "MFH-1 is required for Bone-Morphogenetic Protein-2-induced osteoblastic differentation of C2C12 myoblasts"FEBS Letter. (印刷中).

    • Related Report
      1999 Annual Research Report
  • [Publications] Sugiyama.T.: "Tissue Engineering for Therapeutic Use 3"Elsevier Science B.V.. (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 三浦直行: "Vascular Biology ナビゲーター"メディカルレビュー社. (印刷中)

    • Related Report
      1999 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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