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Detection of genetic alternations in hepatocellular carcinoma tissue by representative difference analysis.

Research Project

Project/Area Number 06670574
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionOSAKA CITY UNIVERSITY

Principal Investigator

NISHIGUCHI Shuhei  Osaka City Univ.Medical School, Assistant Professor, 医学部, 講師 (10192246)

Co-Investigator(Kenkyū-buntansha) TAKEDA Tadashi  Osaka City Univ.Medical School, Assistant Professor, 医学部, 助手 (10254393)
NAKAJIMA Shinya  Osaka City Univ.Medical School, Assistant Professor, 医学部, 講師 (50180287)
Project Period (FY) 1994 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1996: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1995: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1994: ¥700,000 (Direct Cost: ¥700,000)
Keywordshapatocellular carcinoma / representative difference analysis / comparative genomic hybridization / ornithine decarboxylase / interferon regulatory factor-1 / PEST region / hepatocellular carcinoma / 肝癌 / 遺伝子異常 / RDA / ODC / IRF-I / 肝細胞癌 / 癌遺伝子 / オルニチン脱炭酸酵素 / FISH
Research Abstract

During carcinogenesis leading to colon cancer, several genetic alternations accumulate. Vogelatein et al have postulated that such carcinogenesis necessarily involves several steps. In hapatocellular carcinoma, several genetic changes have been identified often in the genes c-myc, c-jun, and p53. That the incidence of these abnormalities in patients is generally low suggests that a more important genetic change in this tumor has probably not yet been identified. We set out to identified still unknown genetic alternations in hepatocellular carcinoma tissue by using representative difference analysis or comparative genomic hybridization. By these methods, we cloned several cDNAs detected in hepatocellular carcinoma tissue but not in liver tissues. The results of experiments were not reproducible. During the experiments, we confirmed certain genetic abnormalities in the ornithine decarboxylase (ODC) and interferon regulatory factor-1 (IRF-1) genes. The expression of mRNA coding for IRF-1 was greater in cancerous tissue, and there was exon skipping in the gene in such tissue. The ODC gene in advanced liver cancer have point mutations that affected the PEST region of the protein. We expressed an ODC clone that had a mutation in PEST region in a reticulocyte lysate ; the half-life of the mutant enzyme protein was prolonged, and its activity was increased compared with wild-type ODC.

Report

(4 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • 1994 Annual Research Report
  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] Tamori A,Nishiguchi S et.al: "Relationship of ornithine decarboxylase activity and histological findings in human hepatocellular carcinoma." Hepatology. 19. 1179-1186 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tamori A Nishiguchi S et al: "Point mutation of ornithine decarboxylase gene in human hepatocellular carcinoma." Cancer Res.55. 3500-3503 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 1.Tamori A., Nishiguchi S,Kuroki T,et al.: "Relationshio of ornithine decarboxylase activity and histological findings in human hepatocellular carcinoma." Hepatology. 19. 1179-1186 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 2.Tamori A., Nishiguchi S,Kuroki T,et al.: "Point mutation of ornithine decarboxylase gene in humen hepoatocellular carcinoma." Canser Res.55. 3500-3503 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tamori A., Nishiguchi S, et al.: "Relationship of ornithine decarboxylase activity and histological findings in human hepatocellular carcinoma." Hepatology. 19. 1179-1186 (1994)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tamori A., Nishiguchi S, et al.: "Point mutation of ornithine decarboxylase gene in human hepoatocellular carcinoma." Cancer Res.55. 3500-3503 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] A.Tamori et al.: "Point Mutation of ornithine decarboxylase gene in human hepatocellular carcinoma." Cancer Res.55. 3500-3503 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Nishiguchi S. et al.: "Relationship of ornithine decarboxylase actinity and histological findings in human hepatocellular carcinoma" Hepatology. 20. 1179-1186 (1994)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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