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FGFRシグナルによる胃癌細胞のCD133およびiPS遺伝子発現制御機構の研究

Research Project

Project/Area Number 23790820
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Gastroenterology
Research InstitutionKinki University

Principal Investigator

松本 和子  近畿大学, 医学部, 助教 (00548456)

Project Period (FY) 2011 – 2012
Project Status Discontinued (Fiscal Year 2011)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsがん幹細胞 / CD133 / FGFRシグナル / 胃癌 / iPS遺伝子
Research Abstract

本研究では、FGFRシグナルによる胃癌細胞株のCD133の発現制御についての検討を行った。胃癌細胞株にFGFRチロシンキナーゼ阻害薬を作用させCD133の発現変化を検討したところ、FGFR2増幅胃癌細胞株は薬剤暴露によりCD133の発現が著明に亢進した。FGFRチロシンキナーゼ阻害薬は、FGFR2増幅胃癌細胞に対して用量および時間依存的にCD133の発現をmRNAレベル、タンパクレベルで亢進させることを明らかにした。さらにFGFRの下流シグナルがCD133の発現に及ぼす影響ついて検討を行った。PI3K阻害薬はCD133の発現変化を認めなかったが、MEK阻害薬はCD133の発現を亢進させた。JNK阻害薬、P38MへPK阻害薬はCD133の発現を変化させなかった。次に、FGFR-MEKシグナルの下流転写因子のCD133発現制御について検討した。FGFRチロシンキナーゼ阻害薬およびMEK阻害薬はともにCD133の発現を亢進させると同時に転写因子であるFOS、FOSL1分子のmRNA発現を低下させ、c-Jun分子のmRNA発現を亢進させていた。それぞれの分子の転写活性を測定したところ、mRNAの発現と相関する結果が得られた。さらにFGFR-MEKシグナルの下流転写因子についてsiRNAを用いて検討した。FosのsiRNAの検討では、FGFRチロシンキナーゼ阻害薬の作用によるcD133の発現変化に有意な変化は認められなかったのに対して、FosL1のsiRNAでは、FGFRチロシンキナーゼ阻害薬によるCD133の発現の亢進を低下させる傾向が認められた。これらの結果より、FGFR2増幅胃癌細胞株におけるCD133の発現は、FGFR-MEKシグナルにより制御されており、胃癌幹細胞の治療標的となると考えられた。

Report

(2 results)
  • 2011 Research-status Report   Annual Research Report
  • Research Products

    (35 results)

All 2013 2012 2011

All Journal Article (19 results) (of which Peer Reviewed: 19 results) Presentation (15 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Gene amplification of ribosomal protein s6 kinase-1 and -2 in gastric cancer.2013

    • Author(s)
      Yoshida S
    • Journal Title

      Anticancer Res

      Volume: 33(2) Pages: 469-75

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] MET amplification as a potential therapeutic target in gastric cancer.2013

    • Author(s)
      Kawakami H
    • Journal Title

      Oncotarget

      Volume: 4(1) Pages: 9-17

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] FGF3/FGF4 amplification and multiple lung metastases in responders to sorafenib in hepatocellular carcinoma.2013

    • Author(s)
      Arao T, Ueshima K, Matsumoto K, Nagai T, Kimura H, Hagiwara S, Sakurai T, Haji S, Kanazawa A, Hidaka H, Iso Y, Kubota K, Shimada M, Utsunomiya T, Hirooka M, Hiasa Y, Toyoki Y, Hakamada K, Yasui K, Kumada T, Toyoda H, Sato S, Hisai H, Kuzuya T, Tsuchiya K, Izumi N, Arii S, Nishio K, Kudo M.
    • Journal Title

      Hepatology

      Volume: 57 Issue: 4 Pages: 1407-1415

    • DOI

      10.1002/hep.25956

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Highly sensitive detection of EGFR T790M mutation using colony hybridization predicts favorable prognosis of patients with lung cancer harboring activating EGFR mutation.2012

    • Author(s)
      Fujita Y
    • Journal Title

      J Thorac Oncol

      Volume: 7(11) Pages: 1640-4

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Slug is upregulated during wound healing and regulates cellular phenotypes in corneal epithelial cells.2012

    • Author(s)
      Aomatsu K
    • Journal Title

      Invest Ophthalmol Vis Sci

      Volume: 53(2) Pages: 751-6

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] SRPX2 is a novel chondroitin sulfate proteoglycan that is overexpressed in gastrointestinal cancer.2012

    • Author(s)
      Tanaka K
    • Journal Title

      Plos One

      Volume: 7(1)

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] FGFR2 gene amplification and clinicopathological featuers in gastric cancer.2012

    • Author(s)
      Matsumoto, K.
    • Journal Title

      Br J Cancer

      Volume: 106(4) Issue: 4 Pages: 727-32

    • DOI

      10.1038/bjc.2011.603

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Plasuma concentrations of angiogenesis-related molecules in patients with pancreatic cancer.2012

    • Author(s)
      Sakamoto H
    • Journal Title

      Jpn J Clin Oncol

      Volume: 42(2) Pages: 105-12

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Integrated analysis of whole genome exon array and array-comparative genomic hybridization in gastric and colorectal cancer cells.2012

    • Author(s)
      Furuta, K.
    • Journal Title

      Cancer Sci

      Volume: 103(2) Issue: 2 Pages: 221-7

    • DOI

      10.1111/j.1349-7006.2011.02132.x

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Aza-derivatives of resveratrol are potent macrophage migration inhibitory factor inhibitors.2012

    • Author(s)
      Fujita Y, de Velasco MA, Nishio K. et. Al.
    • Journal Title

      Invest New Drugs.

      Volume: 30 Issue: 5 Pages: 1878-1886

    • DOI

      10.1007/s10637-011-9749-7

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Expression changes in arrestin β1 and genetic variation in catechol-O-methyltransferase are biomarkers for the response to morphine treatment in cancer patients2011

    • Author(s)
      H.Matsuoka, T.Arao, C.Makimura, M.Takeda, H.Kiyota, J.Tsurutani, Y.Fujita, K.Matsumoto, H.Kimura, M.Otsuka, A.Koyama, CK.Imamura, Y.Tanigawara, T.Yamanaka, K.Tanaka, K.Nishio, K.Nakagawa
    • Journal Title

      Oncology Reports

      Volume: 27(5) Pages: 1393-9

    • DOI

      10.3892/or.2012.1660

    • Related Report
      2011 Research-status Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prospective study evaluating the plasma concentrations of twenty-six cytokines and response to morphine treatment in cancer patients.2011

    • Author(s)
      Makimura C
    • Journal Title

      Anticancer Res

      Volume: 31(12) Pages: 4561-8

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] What can and cannnot be done using a microarray analysis? Treatment stratification and clinical applications in oncology.2011

    • Author(s)
      Arao T
    • Journal Title

      Biol Pharm Bull

      Volume: 34(12) Pages: 1789-93

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Serum heparan sulfate concertration is correlated with the failure of epidermal growth factor receptor tyrosine kinase inhibitor treatment in patients with lung adenocarcinoma.2011

    • Author(s)
      Nishio M
    • Journal Title

      J Thorac Oncol

      Volume: 6(11) Pages: 1889-94

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Activin a inhibits vascular endothelial cell growth and suppresses tumor angiogensis in gastric cancer.2011

    • Author(s)
      Kaneda H
    • Journal Title

      Br J Cancer

      Volume: 105(8) Issue: 8 Pages: 1210-7

    • DOI

      10.1038/bjc.2011.348

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Acquired drug resistanc eto vascular endothelial growth factor receptor 2 tyrosine kinase inhibitor in human vascular endothelial cells.2011

    • Author(s)
      Arao T
    • Journal Title

      Anticancer Res

      Volume: 31(9) Pages: 2787-96

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Sorafenib inhibits the hepatocyte growth factor-mediated epithelial mesenchymal transition in hepatocellular carcinoma.2011

    • Author(s)
      Nagai T
    • Journal Title

      Mol Cancer Ther

      Volume: 10(1) Pages: 169-77

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] TGF-β induces sustained upregulation of SNAI1 and SNAI2 through Smad and non-Smad pathways in a human corneal epithelial cell line.2011

    • Author(s)
      Aomatsu K
    • Journal Title

      Invest Ophthalmol Vis Sci

      Volume: 52(5) Pages: 2437-43

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Antitumor activity of BIBF 1120, a triple angiokinase inhibitor, and use of VEGFR2+pTyr+ peripheral blood leukocytes as a pharmacodynamic biomarker in vivo.2011

    • Author(s)
      Kudo K
    • Journal Title

      Clin Cancer Res

      Volume: 17(6) Pages: 1373-81

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] Frequency of FGFR2 Gene Amplification in Gastric Cancer2012

    • Author(s)
      Matsumoto, K
    • Organizer
      American Association for Cancer Research 103nd Annual
    • Place of Presentation
      Chicago, IL
    • Related Report
      2011 Annual Research Report
  • [Presentation] 胃がんにおけるFGFR2遺伝子増幅の検討2012

    • Author(s)
      松本和子
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      ロイトン不L幌、さっぽろ芸文館他(札幌市)
    • Related Report
      2011 Annual Research Report
  • [Presentation] FGFR阻害薬によるCD133の発現制御機構の解析2012

    • Author(s)
      松本和子
    • Organizer
      第10回日本臨床腫瘍学会学術集会
    • Place of Presentation
      大阪国際会議場(大阪市)
    • Related Report
      2011 Annual Research Report
  • [Presentation] FGFR2増幅胃癌の解析2012

    • Author(s)
      松本和子
    • Organizer
      第16回 日本がん分子標的治療学会学術集会
    • Place of Presentation
      西日本総合展示場(北九州市)
    • Related Report
      2011 Annual Research Report
  • [Presentation] Aza-derivatives of resveratrol are inhibitors of macrophage migration inhibitory factor (MIF).2011

    • Author(s)
      Fujita, Y
    • Organizer
      American Association for Cancer Research 102nd Annual Meeting 2011
    • Place of Presentation
      Florida
    • Related Report
      2011 Research-status Report
  • [Presentation] Somatic mutation profiling to tumor samples using OncoCarta Panel.2011

    • Author(s)
      Furuta, K.
    • Organizer
      American Association for Cancer Research 102nd Annual Meeting 2011
    • Place of Presentation
      Florida
    • Related Report
      2011 Research-status Report
  • [Presentation] Expression levels of EMT-related genes in hepatocellular carcinoma.2011

    • Author(s)
      Nagai, T.
    • Organizer
      American Association for Cancer Research 102nd Annual Meeting 2011
    • Place of Presentation
      Florida
    • Related Report
      2011 Research-status Report
  • [Presentation] Slug-mediated epithelial mesenchymal transition in lugn cancer cells.2011

    • Author(s)
      Tamura, D.
    • Organizer
      American Association for Cancer Research 102nd Annual Meeting 2011
    • Place of Presentation
      Florida
    • Related Report
      2011 Research-status Report
  • [Presentation] FGFR inhibitor regulates CD133 expression in FGFR2-amplified gastric cancer cells.2011

    • Author(s)
      Matsumoto, K.
    • Organizer
      American Association for Cancer Research 102nd Annual Meeting 2011
    • Place of Presentation
      Florida
    • Related Report
      2011 Research-status Report
  • [Presentation] Serum concentrations of angiogenesis-related molecules in patients with pancreatic cancer.2011

    • Author(s)
      Kimura, H.
    • Organizer
      American Association for Cancer Research 102nd Annual Meeting 2011
    • Place of Presentation
      Florida
    • Related Report
      2011 Research-status Report
  • [Presentation] An analysis of serum heparan sulfate concentration and EGFR tyrosine kinase inhibitor treatment in patients with non-small cell lung adenocarcinoma.2011

    • Author(s)
      Nishio, M.
    • Organizer
      American Society of Clinical Oncology Annual Meeting 2011
    • Place of Presentation
      Chicago
    • Related Report
      2011 Research-status Report
  • [Presentation] 血清ヘパラン硫酸濃度とEGRチロシンキナーゼ阻害薬耐性2011

    • Author(s)
      松本和子
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋市
    • Related Report
      2011 Research-status Report
  • [Presentation] 大腸がんにおけるHS6ST2発現とその臨床的特徴2011

    • Author(s)
      木村英晴
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋市
    • Related Report
      2011 Research-status Report
  • [Presentation] 肝細胞癌におけるTJP-1とTwist発現の肝癌切除後の予後への影響2011

    • Author(s)
      永井知行
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋市
    • Related Report
      2011 Research-status Report
  • [Presentation] 非小細胞肺がんにおけるEGFR T790の変異の新規検出法2011

    • Author(s)
      藤田至彦
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋市
    • Related Report
      2011 Research-status Report
  • [Patent(Industrial Property Rights)] ソラフェニブの効果予測方法2011

    • Inventor(s)
      松本和子、他
    • Industrial Property Rights Holder
      近畿大学、他
    • Industrial Property Number
      2011-104275
    • Filing Date
      2011
    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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