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デジタル ゲノム スキャニング法の開発と胃癌関連遺伝子探索への応用

Research Project

Project/Area Number 19659344
Research Category

Grant-in-Aid for Exploratory Research

Allocation TypeSingle-year Grants
Research Field Digestive surgery
Research InstitutionSapporo Medical University

Principal Investigator

時野 隆至  Sapporo Medical University, 医学部, 教授 (40202197)

Co-Investigator(Kenkyū-buntansha) 古畑 智久  札幌医科大学, 医学部, 准教授 (80359992)
見田 裕章  札幌医科大学, 医学部, 助教 (90347162)
明石 浩史  札幌医科大学, 医学部, 講師 (60336386)
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2008: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2007: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywords癌 / ヒトゲノム / 遺伝子増幅 / 遺伝子欠失 / 癌(がん)
Research Abstract

癌遺伝子の増幅や癌抑制遺伝子の欠失を伴う染色体変化は癌細胞の特徴である.本研究では短いゲノム断片を解析しゲノム上のDNAコピー数以上を示す領域を検出する方法としてデジタルゲノムスキャニング(DGS: Digital Genome Scanning)法を開発し,胃癌細胞株におけるゲノムコピー数異常の検出を試みた.
DGS法を利用して,ヒト胃癌細胞株においてKRASCACNAIC (calcium channel, viltage-dependent, 1 type, alpha-1c subunit)を含む2つの約500kbのゲノム領域を染色体12p12.1と12p13.33に同定した.KRAS遺伝子増幅を有する胃癌細胞株では,KRASのmRNAおよびタンパクレベルはKRAS遺伝子コピー数とよく相関していた.正常型KRASが遺伝子増幅した胃癌細胞では,血清刺激後に高レベルのGTP-KRASおよびリン酸化p44/42が検出された.一方,変異型KRASが遺伝子増幅した別の胃癌細胞では,恒常的に高レベルの活性型KRASおよびp44/42が検出された.この結果は,細胞増殖において正常型KRASの遺伝子増幅が無刺激条件下で選択優位性をもたらすのみならず,増殖因子刺激や高栄養環境の条件では点変異KRAS遺伝子と同様に著しい選択優位性を獲得可能なことを強く示唆している.
以上より,DGS法は癌を代表とするゲノムコピー数異常を呈する疾患の原因遺伝子探索において有効な手法となりうることを実証した.

Report

(2 results)
  • 2008 Annual Research Report
  • 2007 Annual Research Report
  • Research Products

    (33 results)

All 2009 2008 2007

All Journal Article (31 results) (of which Peer Reviewed: 30 results) Presentation (2 results)

  • [Journal Article] p53 family members regulate the expression of the apolipoprotein D gene.2009

    • Author(s)
      Sasaki Y, et al
    • Journal Title

      J Biol Chem 284

      Pages: 872-883

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A single recombinant adenovirus expressing p53 and p21-targeting artificial microRNAa efficiently induces apoptosis in human cancer cells.2009

    • Author(s)
      Idogawa M, et al
    • Journal Title

      Clinical Cancer Research (印刷中)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cancer epigenomics : Implications of DNA methylation in personalized cancer therapy.2009

    • Author(s)
      Toyota M, et al
    • Journal Title

      Cancer Science (印刷中)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The histone deacetylase inhibitor FK228 enhances adenovirus-mediated p53 family gene therapy in cancer models.2008

    • Author(s)
      Sasaki Y, et al
    • Journal Title

      Molecular Cancer Therapeutics 7

      Pages: 779-787

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of flotillin-2, a major protein on lipid rafts, as a novel target of the p53 family members.2008

    • Author(s)
      Sasaki Y, et al
    • Journal Title

      Molecular Cancer Research 6

      Pages: 395-406

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Epigenetic silencing of microRNA-34b/c and BTG4 is associated with CpG island methylation in colorectal cancer.2008

    • Author(s)
      Toyota M, et al
    • Journal Title

      Cancer Research 68

      Pages: 4124-4132

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A requirment for DICER to maintain full promoter CpG island hypermethylation in human cancer cells.2008

    • Author(s)
      Ting AH, et al
    • Journal Title

      Cancer Research 68

      Pages: 2570-2575

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cytoplasmic RASSF2A is a pro-appoptotic mediator whose expression is epigenetically silenced in gastric cancer.2008

    • Author(s)
      Maruyama R, et al
    • Journal Title

      Carcinogenesis 29

      Pages: 1312-1318

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Frequent epigenetic inactivation of Wnt antagonist genes in breast cancer.2008

    • Author(s)
      Suzuki H, et al
    • Journal Title

      British J Cancer 98

      Pages: 1147-1156

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] DNA methylation and cancer pathways in gastrointestinal tumors.2008

    • Author(s)
      Suzuki H, et al
    • Journal Title

      Pharmacogenomics 9

      Pages: 1917-1928

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Epigenetic inactivation of RASSF2 in oral squamous cell carcinoma.2008

    • Author(s)
      Imai T, et al
    • Journal Title

      Cancer Science 99

      Pages: 958-966

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Epigenetic inactivation of SFRP genes in oral squamous cell carcinoma.2008

    • Author(s)
      Sogabe Y, et al
    • Journal Title

      Int J Oncology 32

      Pages: 1253-1261

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] DNA hypermethylation causes incomplete systhesis of carbohydrate determinants in gastrointestinal cancer.2008

    • Author(s)
      Kawamura YI, et al
    • Journal Title

      Gastroenterology 135

      Pages: 142-151

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Frequent epigenetic inactivation of SFRP genes in hepatocellular carcinoma.2008

    • Author(s)
      Takagi H, et al
    • Journal Title

      J Gastroenterol 43

      Pages: 378-389

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] LINE-1 hypomethylation is associated with increased CpG island methylation in Helicobactor pylori-related enlarged-fold gastritis.2008

    • Author(s)
      Yamamoto E, et al
    • Journal Title

      Cancer Epidemiol Biomakers Prev 17

      Pages: 2555-2564

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In vitro transformation of adult rat hepatic progenitor cells into pancreatic endocrine hormone-producing cells.2008

    • Author(s)
      Kawasaki H, et al
    • Journal Title

      J Hepatobiliary Pancreat Surg 15

      Pages: 310-317

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prediction of p53 target genes based on integrative analysis of chromatin-immunoprecipitated and sequenced tags, by using Galaxy, a web-based interactive platform for large-scale genome analysis.2008

    • Author(s)
      Mita H, et al
    • Journal Title

      Tumor Research 43

      Pages: 1-23

    • Related Report
      2008 Annual Research Report
  • [Journal Article] Identification of flotillin-2, a major protein on lipid rafts, as a novel target of the p53 family members.2008

    • Author(s)
      Sasaki Y
    • Journal Title

      Molecular Cancer Research 6

      Pages: 395-406

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] DNA hypermethylation causes incomplete systhesis of carbohydrate determinants in gastrointestinal cancer.2008

    • Author(s)
      Kawamura YI
    • Journal Title

      Gastroenterology (印刷中)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The histone deacetylase inhibitor FK228 enhances adenovirus-mediated p53 family gene therapy in cancer models.2008

    • Author(s)
      Sasaki Y
    • Journal Title

      Molecular Cancer Therapeutics (印刷中)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Frequent epigenetic inactivation of Wnt antagonist genes in breast cancer.2008

    • Author(s)
      Suzuki H
    • Journal Title

      British J Cancer (印刷中)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cytoplasmic RASSF2A is a pro-appoptotic mediator whose expression is epigenetically silenced in gastric cancer.2008

    • Author(s)
      Maruyama R
    • Journal Title

      Carcinogenesis (印刷中)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Epigenetic inactivation of RASSF2 in oral squamous cell carcinoma.2008

    • Author(s)
      Imai T
    • Journal Title

      Cancer Science (印刷中)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Epigenetic inactivation of SFRP genes in oral squamous cell carcinoma.2008

    • Author(s)
      Sogabe Y
    • Journal Title

      Int J Oncology (印刷中)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ku70 and poly (ADP-ribose) polymerase-1 competitively regulate beta-catenine and T-cell factor-4-mediated gene transactivation: possible linkage of DNA damage recognition and Wnt signaling.2007

    • Author(s)
      Idogawa M
    • Journal Title

      Cancer Research 67

      Pages: 911-918

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gene Amplification and overexpression of PRDM14 in breast cancers.2007

    • Author(s)
      Nishikawa N
    • Journal Title

      Cancer Research 67

      Pages: 9649-9657

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Frequent epigenetic inactivation of SFRP genes and constitutive activation of Wnt signaling in gastric cancer.2007

    • Author(s)
      Nojima M
    • Journal Title

      Oncogene 26

      Pages: 4699-4713

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression profiling of PRDM famiy genes identified PRDM5 as a target of epigenetic silencing in colorectal and gastric cancer.2007

    • Author(s)
      Watanabe Y
    • Journal Title

      Clinical Cancer Research 13

      Pages: 4786-4794

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Frequent epigenetic inactivation of DICKKOPF family genes in human gastrointestinal tumors.2007

    • Author(s)
      Sato H
    • Journal Title

      Carcinogenesis 28

      Pages: 2459-2466

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of DFNA5 as a target of epigenetic inactivation in gastric cancer.2007

    • Author(s)
      Akino K
    • Journal Title

      Cancer Science 98

      Pages: 88-95

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Antitumor effect of adenovirus-mediated p53 family gene transfer on osteosarcoma cell lines.2007

    • Author(s)
      Oshima Y
    • Journal Title

      Cancer Biology & Therapy 6

      Pages: 1058-1066

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] Antitumor effect of adenovirus-mediated p53 family gene transfer on osteosarcoma cell lines.2008

    • Author(s)
      時野隆至
    • Organizer
      米国癌学会年会
    • Place of Presentation
      米国ロサンゼルス
    • Year and Date
      2008-04-17
    • Related Report
      2008 Annual Research Report
  • [Presentation] Antitumor effect of adenovirus-mediated p53 family gene transfer on osteosarcoma cell lines.2007

    • Author(s)
      時野 隆至
    • Organizer
      米国癌学会
    • Place of Presentation
      米国ロサンゼルス
    • Year and Date
      2007-04-17
    • Related Report
      2007 Annual Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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