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Genome-wide screen for hepermethylated genes in hepatocellular carcinoma

Research Project

Project/Area Number 13670490
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionChiba University

Principal Investigator

IMAZEKI Fumio  Chiba University, Graduate School of Medicine, Lecturer, 大学院・医学研究院, 講師 (40223325)

Co-Investigator(Kenkyū-buntansha) YOKOSUKA Osamu  Chiba University, Graduate School of Medicine, Lecturer, 大学院・医学研究院, 講師 (90182691)
深井 健一  千葉大学, 医学部・付属病院, 医員
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2001: ¥1,700,000 (Direct Cost: ¥1,700,000)
Keywordshepatocellular carcinoma / cDNA microarray / DNA methylation / 5-aza-2'deoxycytidine / CpG island / メチル化 / CpG island / Aza-C
Research Abstract

Gene silencing due to aberrant DNA methylation causes inactivation of tumor suppressor genes, which plays an important role during carcinogenesis. Expression of p16INK4a gene was suppressed due to aberrant DNA methylation in hepatocellular carcinoma and other novel genes could be suppressed by the same mechanism. Therefore, we analyzed gene expression profile altered after DNA methyltransferase inhibitor, 5-aza-2' deoxycytidine (5Aza-dC) treatment using cDNA microarray in 6 hepatome cell lines. Among 14 genes exhibiting the substantial induction (more than 5-fold changes) after 5Aza-dC treatment in multiple hepatoma cell lines, based on cDNA microarray analysis, 6 genes including hepatocyte growth factor activator inhibitor 2 (HAI2), E-cadherin, collagen type 1 alpha 2 (COL1A2), insulin-like growth factor binding protein 2 (IGFBP2), connective tissue growth factor (CTGF) and fibronectin 1 (FN1) exhibited hypermethylation of CpG islands on hepatoma cells. In further studies of primary hepatoma tissues using methylation-specific PCR (MS-PCR), hypermethylation of HAI2 was detected in tumorous tissues more often than in corresponding nontumorous tissues. In conclusion, we could identify 6 hypermethylated genes in hepatoma by microarray based strategy. Aberrant methylation of HAI2 gene might be involved in hepatocarcinogenesis due to overexpression of hepatocyte growth factor.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (9 results)

All Other

All Publications (9 results)

  • [Publications] Sumi H, et al.: "Influence of hepatitis B virus genotypes on the progression of chronic type B liver disease"Hepatology. 37. 19-26 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawai S, et al.: "Evaluation of the clinical usefulness of COBAS AMPLICOR HCV MONITOR assay (ver2.0) : Comparison with AMPLICOR HCV MONITOR assay (ver1.0) and HCV core protein level"J Med Virol.. 68. 343-351 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawai S, et al.: "State of HBV DNA in HBsAg-negative, anti-HCV-positive hepatocellular carcinoma : existence of HBV DNA possibly as nonintegrated form with analysis by Alu-HBV DNA PCR and conventional HBV PCR"J Med Virol.. 64. 410-418 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sumi H, et al.: "Influence of hepatitis B virus genotypes on the progression of chronic type B liver disease"Hepatology. 37. 19-26 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawai S, et al.: "Evaluation of the clinical usefulness of COBAS AMPLICOR HCV MONITOR assay (ver2.0) : Comparison with AMPLICOR HCV MONITOR assay (ver1.0) and HCV core protein level"J Med Virol. 68. 343-351 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawai S, et al.: "State of HBV DNA in HBsAg-negative, anti-HCV-positive hepatocellular carcinoma : existence of HBV DNA possibly as nonintegrated form with analysis by Alu-HBV DNA PCR and conventional HBV PCR"J Med Virol.. 64. 410-418 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sumi H, et al.: "Influence of hepatitis B virus genotypes on the progression of chronic type B liver disease"Hepatology. 37・1. 19-26 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kawai S, et al.: "Evaluation of the clinical usefulness of COBAS AMPLICOR HCV MONITOR assay (ver2.0) : Comparison with AMPLICOR HCV MONITOR assay (ver1.0) and HCV core protein level"J Med Virol.. 68・3. 343-351 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kawai S, et al.: "State of HBV DNA in HBsAg-negative, anti-HCV-positive hepatocellular carcinoma : existence of HBV DNA possibly as nonintegrated form with analysis by Alu-HBV DNA PCR and conventional HBV PCR"J Med Virol. 64・4. 410-418 (2001)

    • Related Report
      2002 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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