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SAGEライブラリーに基づいた新規消化管癌特異遺伝子の抽出と個性診断への応用

Research Project

Project/Area Number 17015031
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionHiroshima University

Principal Investigator

安井 弥  広島大学, 大学院医歯薬学総合研究科, 教授 (40191118)

Project Period (FY) 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥8,200,000 (Direct Cost: ¥8,200,000)
Fiscal Year 2005: ¥8,200,000 (Direct Cost: ¥8,200,000)
Keywords消化管癌 / SAGEライブラリー / 個性診断 / ELISA / REGIV / MIA / MMP-10 / カスタムアレイ
Research Abstract

SAGEライブラリーの比較から新しい癌特異的遺伝子を抽出し、標的治療を視野に入れた消化管癌の診断系を確立することを目的として以下のとおり実施した。
1)消化管癌と正常臓器のSAGEライブラリーの比較による新規癌特異的遺伝子の抽出:我々の胃癌SAGEライブラリー(GEO accession no.GSE545)と主要14臓器(心臓、肺、肝臓、脳など)のそれとの比較および定量的RT-PCR法により、APIN,TRAG3,CYP2W1,MIA,MMP-10,DKK4,GW112,REGIV,HORMAD1の9遺伝子が胃癌特異的であることを見い出した。食道扁平上皮癌についてSAGEライブラリーを作成し、正常食道のそれと比較して発現の異なる遺伝子群を抽出した。
2)Recombinant蛋白の調整、抗体作成およびELISA系の構築:抗体の入手可能であったMIA,DKK4,MMP-10および独自にポリクローナル抗体を作成したREGIVでは、免疫染色およびELISAを行い、MIAとMMP-10の組織内発現が悪性度と相関すること、REGIVとMMP-10がよい血清マーカーであることを見い出した。他の遺伝子については順次recombinant蛋白の調整、モノクローナル抗体の作成を行い、特異性を確認中である。
3)新規癌特異的発現遺伝子の機能解析:REGIVの胃癌細胞株強制発現系で、5-FUによるアポトーシスの抑制を明らかにした。さらに、数種の細胞質内および核内蛋白と相互作用を示すことを見い出すとともに、動物モデル系において腹膜播種を促進することを明らかにした。
4)SAGEライブラリーに基づいたカスタムオリゴDNAアレイの作成とそれによる検索:上記で抽出した癌特異的発現遺伝子を加えた約200遺伝子を搭載する三次元カスタムアレイを新たに作成し、約20症例の胃癌を解析し臨床病理学的事項との検討を行った。

Report

(1 results)
  • 2005 Annual Research Report
  • Research Products

    (13 results)

All 2006 2005

All Journal Article (12 results) Book (1 results)

  • [Journal Article] Accumulation of DNA methylation is associated with tumor stage in gastric cancer2006

    • Author(s)
      Oue, N.
    • Journal Title

      Cancer (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Systematic search for gastric cancer-specific genes based on SAGE data : melanoma inhibitory activity and matrix metalloproteinase-10 are novel prognostic factors in patients with gastric cancer2006

    • Author(s)
      Aung, PP.
    • Journal Title

      Oncogene (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Down-regulation of the claudin-18 gene, identified through serial analysis of gene expression data analysis, in intestinal phenotype of gastric cancer2006

    • Author(s)
      Sanada, Y.
    • Journal Title

      J.Pathol. (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Glycogen synthase kinase-3 and H-prune regulate cell migration by modulating focal adhesions2006

    • Author(s)
      Kobayashi, T.
    • Journal Title

      Mol.Cell Biol. 26

      Pages: 898-911

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Loss of heterozygosity and histone hypoacetylation of the PINX1 gene are associated with reduced expression in gastric carcinoma2005

    • Author(s)
      Kondo, T.
    • Journal Title

      Oncogene 24

      Pages: 157-164

    • Related Report
      2005 Annual Research Report
  • [Journal Article] A single nucleotide polymorphism in the 5'untranslated region of EGF gene is associated with occurrence and malignant progression of gastric cancer2005

    • Author(s)
      Hamai, Y.
    • Journal Title

      Pathobiol. 72

      Pages: 133-138

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Genes involved in invasion and metastasis of gastric cancer identified by array-based hybridization and serial analysis of gene expression2005

    • Author(s)
      Oue, N.
    • Journal Title

      Oncology 69S1

      Pages: 17-22

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Quantitative analysis of lymphangiogenic markers for predicting metastasis of human gastric carcinoma to lymph nodes2005

    • Author(s)
      Kitadai, Y.
    • Journal Title

      Int.J.Cancer 115

      Pages: 388-392

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Clinicopathological significance and prognostic influence of cadherin-17 expression in gastric cancer2005

    • Author(s)
      Ito, R.
    • Journal Title

      Virchow Arch. 447

      Pages: 717-722

    • Related Report
      2005 Annual Research Report
  • [Journal Article] DNA methylation profile in differentiated type gastric carcinoma with distinct mucin phenotypes2005

    • Author(s)
      Motoshita, J.
    • Journal Title

      Cancer Sci. 96

      Pages: 474-479

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Expression and localization of RegIV in human neoplastic and non-neoplastic tissues : RegIV expression is associated with intestinal and neuroendocrine differentiation in gastric adenocarcinoma.2005

    • Author(s)
      Oue, N.
    • Journal Title

      J.Pathol. 207

      Pages: 185-198

    • Related Report
      2005 Annual Research Report
  • [Journal Article] DNA methylation of genes linked with retinoid signaling in gastric cance r: expression of retinoic acid receptorβ, cellular retinol binding protein 1and tazarotene-induced gene 1 is associated with DNA methylation2005

    • Author(s)
      Shutoh, M.
    • Journal Title

      Cancer 104

      Pages: 1609-1619

    • Related Report
      2005 Annual Research Report
  • [Book] The Diversity of Gastric Carcinoma : Pathogenesis, Diagnosis, and Therapy2005

    • Author(s)
      Yasui, W.
    • Total Pages
      353
    • Publisher
      Springer-Verlag
    • Related Report
      2005 Annual Research Report

URL: 

Published: 2005-04-01   Modified: 2018-03-28  

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