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Inflammation-caused abnormalities in gastric differentiation and molecular epidemiologic analysis of gastric cancer

Research Project

Project/Area Number 16390168
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Hygiene
Research InstitutionTokyo Medical and Dental University

Principal Investigator

YUASA Yasuhito  Tokyo Medical and Dental University, Department of Molecular Oncology, Professor, 大学院・医歯学総合研究科, 教授 (80111558)

Co-Investigator(Kenkyū-buntansha) AKIYAMA Yoshimitsu  Tokyo Medical and Dental University, Department of Molecular Oncology, lecturer, 大学院・医歯学総合研究科, 講師 (80262187)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥15,000,000 (Direct Cost: ¥15,000,000)
Fiscal Year 2005: ¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 2004: ¥8,500,000 (Direct Cost: ¥8,500,000)
Keywordsdifferentiation / gastric cancer / SOX2 / Mucin / Notch / Hath-1 / MUC6 / apoptosis / 炎症 / メチル化 / DNMT3A / NFκB / Sp1 / CDX2 / 胆嚢がん
Research Abstract

1. Transcription factor SOX2 up-regulates stomach- specific pepsinogen A gene expression
SOX2 is expressed in normal gastric mucosae but not in the normal colon. To clarify the role of SOX2, we analyzed expression of SOX2 and pepsinogens, differentiation markers of the stomach, in 10 gastric cancer (GC) and 10 colorectal cancer (CRC) cell lines. Six GC and five CRC cell lines showed SOX2 expression on RT-PCR. Expression of pepsinogen A was detectable in 8 GC and 7 CRC cell lines, whereas the majority of the cell lines expressed pepsinogen C. Over-expression of SOX2 up-regulated expression of endogenous pepsinogen A but not that of pepsinogen C in GC and CRC cell lines. Moreover, pepsinogen A expression was significantly reduced by SOX2 RNA interference in GC cell lines. These data suggest that SOX2 plays an important role in regulation of pepsinogen A, and ectopic expression of SOX2 may be associated with abnormal differentiation of colorectal cancer cells.
2. Hath1 up-regulates gastric … More mucin gene expression in gastric cells
The Notch signaling pathway is known to mediate cell differentiation. We investigated mRNA expression of seven Notch-related genes, and compared it with expression of gastric mucin genes, MUC5AC and MUC6, in 8 gastric cancer (GC) cell lines. Notch1/2/3 and Hes1 were expressed in most GC cell lines as well as normal gastric mucosae, while Hes2/3 were expressed in neither these cell lines nor the normal stomach. As for Hath1, 5 GC cell lines exhibited undetectable levels, while normal gastric mucosa expressed Hath1. The expression patterns of Hath1 and MUC6 were closely related in most GC cell lines. Many MUC5AC-positive cases also tended to show Hath1 expression. Over-expression of Math1 in the GC cells enhanced both the MUC6 and MUC5AC mRNA levels. Knockdown of Hath1 by RNA interference significantly decreased expression of both mucin genes. These data indicate that Hath1 is one of the transcriptional regulators for MUC6 and MUC5AC in GC cells. It is also possible that loss of Hath1 expression may play a role in gastric carcinogenesis. Less

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (23 results)

All 2006 2005 2004 Other

All Journal Article (22 results) Book (1 results)

  • [Journal Article] Frequent epigenetic silencing of the bone morphogenetic protein 2 gene by methylation in gastric carcinomas.2006

    • Author(s)
      Wen X-Z, et al.
    • Journal Title

      Oncogene (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Involvement of GATA-4/-5 transcription factors in ovarian carcinogenesis.2006

    • Author(s)
      Wakana K, et al.
    • Journal Title

      Cancer Letters (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Relationship between CDX2 gene methylation and dietary factors in gastric cancer patients.2005

    • Author(s)
      Yuasa Y, et al.
    • Journal Title

      Carcinogenesis 26

      Pages: 193-200

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Transcriptional regulation of the human DNA methyltransferase 3A and 3B genes by Sp3 and Sp1 zinc finger proteins.2005

    • Author(s)
      Jinawath A, et al.
    • Journal Title

      Biocemical J. 385

      Pages: 557-564

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] A novel EID family member, EID-3, forms a homodimer or heterodimer with EID-2.2005

    • Author(s)
      Sasajima Y, et al.
    • Journal Title

      Biochem. Biophys. Res. Commun. 333

      Pages: 969-975

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Upregulation of MUC6 mucin gene expression by NF- kB and Sp factors.2005

    • Author(s)
      Sakai H, et al.
    • Journal Title

      Biochem. Biophys. Res. Commun. 333

      Pages: 1254-1260

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Expression of homeodomain protein CDX2 in gallbladder carcinomas.2005

    • Author(s)
      Wu XS, et al.
    • Journal Title

      J. Cancer Res. Clin. Oncology 131

      Pages: 271-278

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Requirement of the MAP kinase signaling pathways for mouse preimplantation development.2005

    • Author(s)
      Maekawa M, et al.
    • Journal Title

      Development 132

      Pages: 1773-1783

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Transcriptional regulation of the human DNA methyltransferase 3A and 3B genes by Sp3 and Sp1 zinc finger proteins.2005

    • Author(s)
      Jinawath A, et al.
    • Journal Title

      Biochemical J. 385

      Pages: 557-564

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A novel EID family member, EID-3, forms a homodimer or heterodimer with EID-2.2005

    • Author(s)
      Sasajima Y, et al.
    • Journal Title

      Biochem.Biophys.Res.Commun. 333

      Pages: 969-975

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Upregulation of MUC6 mucin gene expression by NF-κB and Sp factors.2005

    • Author(s)
      Sakai H, et al.
    • Journal Title

      Biochem.Biophys.Res.Commun. 333

      Pages: 1254-1260

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Expression of homeodomain protein CDX2 in gallbladder carcinomas.2005

    • Author(s)
      Wu XS, et al.
    • Journal Title

      J.Cancer Res.Clin.Oncology 131

      Pages: 271-278

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Inactivation of the tissue inhibitor of metallortoteinases-2 gene by promoter hypermethylation in lymphoid malignancies.2005

    • Author(s)
      Galm O, et al.
    • Journal Title

      Oncogene 24

      Pages: 4799-4805

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Upregulation of MUC6 mucin gene expression by NF-kB and Sp factors.2005

    • Author(s)
      Sakai H, et al.
    • Journal Title

      Biochem.Biophys.Res.Commun. 333

      Pages: 1254-1260

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Transcriptionalregulation of the human DNA methyltransferase 3A and 3B genes by Sp3 and Sp1 zinc finger proteins.2005

    • Author(s)
      Jinawath A, et al.
    • Journal Title

      Biocemical J. 385

      Pages: 557-564

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Expression of the SRY-related HMG box protein SOX2 in human gastric carcinoma.2004

    • Author(s)
      Li X-L, et al.
    • Journal Title

      Int.J.Oncology 24

      Pages: 257-263

    • Related Report
      2004 Annual Research Report
  • [Journal Article] PDX1 homeobox protein expression in pseudopyloric glands and gastric carcinomas.2004

    • Author(s)
      Sakai H, et al.
    • Journal Title

      Gut 53

      Pages: 323-330

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Transcription factor GATA-5 selectively up-regulates mucin gene expression.2004

    • Author(s)
      Ren C-Y, et al.
    • Journal Title

      J.Cancer Res.Clin.Oncology 130

      Pages: 245-252

    • Related Report
      2004 Annual Research Report
  • [Journal Article] BMP-2 modulates the proliferation and differentiation of normal and cancerous gastric cells.2004

    • Author(s)
      Wen X-Z, et al.
    • Journal Title

      Biochem.Biophys.Res.Commun. 316

      Pages: 100-106

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Frequent epigenetic silencing of the bone morphogenetic protein 2 gene by methylation in gastric carcinomas.

    • Author(s)
      Wen X-Z, et al.
    • Journal Title

      Oncogene (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Involvement of GATA-4/-5 transcription factors in ovarian carcinogenesis.

    • Author(s)
      Wakana K, et al.
    • Journal Title

      Cancer Letters (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Hath1 up-regulates gastric mucin gene expression in gastric cells.

    • Author(s)
      Sekine A, et al.
    • Journal Title

      Biochem.Biophys.Res.Commun. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] がん予防の最前線 下巻2005

    • Author(s)
      湯浅保仁(分担執筆)
    • Total Pages
      226
    • Publisher
      昭和堂
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary

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Published: 2004-04-01   Modified: 2016-04-21  

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