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Hepatocarcinogesis and Genomic Instability: Functional Analysis of Y-box binding protein.

Research Project

Project/Area Number 12670537
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionJapanese Foundation for Cancer Research

Principal Investigator

KAJINO Kazunori  Cancer Institute, Dept. of Exp. pathology, Associate, 癌研究所・実験病理部, 研究員 (80260066)

Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2000: ¥2,000,000 (Direct Cost: ¥2,000,000)
KeywordsHypercarcinogenic State / Genomic instability / Hepatitles B virus / DNA recombination
Research Abstract

We isolated dbpA, a member of the Y-box binding protein family, as the candidate for the cellular protein inducing genomic instability. We obtained the following findings about dbpA.
1.DbpA expressed in E.coli showed the weak strand exchange activity. Recently, YB-i, another member of this family, is reported to have the annealing activity of DNA or RNA (JBC 276 : 4484 1-44847), and the possible association of this family with DNA recombination is suggested by their work as well as by ours.
2.We raised anti-dbpA Ab which recognized dbpA expressed in E.coli with high sensitivity. At present, we are examining the expression of dbpA in various cancer tissue. (In the level of transcripts, the enhanced expression is already confirmed in HCC.)
3.We made Transgenic mouse where dbpA is. to be overexpressed in liver. We are going to examine its susceptibility to HCC.
4.Using anti-YB-l Ab, we checked its expression in various human tissues. Enhanced expression was detected in several normal tissues including gastrointestinal epithelium, as well as in HCC.
5.By replacing T with G at nt -5 of dbpA promoter region, the promoter activity increased twofold. The identical replacement was detected in 3 of 51 HCC cases. We detected the 25 kDa cellular protein which specifically bind to the promoter region with T to A conversion, and currently on the way to identify it.

Report

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

    (10 results)

All Other

All Publications (10 results)

  • [Publications] Kajino K: "Recombination hat spot of hepatitis B virus genome binds to members of the HMV domain protein and the Y box binding protein family : Implication of these proteins in genomic Instability"Intervirology. Vol.44. 311-316 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kajino K: "Similarity of the secondary structure with identical seven bases in the pregenomic/genomic regions required for the replication of hepatitis B virus and hepatuis C virus"Proceedings of the Japan Academy. Vol.78. 12-14 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 梶野一徳: "肝発癌とゲノム不安定性"日本臨床. 59巻. 112-115 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kajino K: "Recombination hot spot of hepatitis B virus genome binds to members of the HMG domain protein and the Y box binding protein family : Implication of these proteins in genomic instability."Intervirology. Vol.44. 311-316 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kajino K: "Similanty of the secondary structure with identical seven bases in the pregenomic/genomic regions reguired for the replication of hepatitis B virus and hepatitis C virus"Proceeding of the Japan Academy. Vol.78. 12-14 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kajino K: "Hepatocarcinogenesis and genomic instability."Nihon Rinsho. Vol.59. 112-115 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kajino K: "Recombination hot spot of hepatitis B virus genome binds to members of the HMV domain protein and the Y box binding protein family : Implication of these proteins in genomic instability"Intervirology. vol.44. 311-316 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kajino K: "Similarity of the secondary structure with Identical seven bases In the pregenomic/genomic regions required for the replication of hepatitis 13 virus and hepatitis C virus"Proceedings of the Japan Academy. vol.78. 12-14 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 梶野一徳: "肝発癌とゲノム不安定性"日本臨床. 59巻. 112-115 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hayashi J: "Hepatitis C virus core protein activates the MAPK/ERK cascade synergistically with tumor promoter TPA, but not with epidermal growth factor or transforming growth factor alpha."Hepatology. vol 32,no 5. 958-961 (2000)

    • Related Report
      2000 Annual Research Report

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

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