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Establishment and characterization for imatinib-resistant GIST cell lines from patients

Research Project

Project/Area Number 22791302
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Digestive surgery
Research InstitutionKeio University

Principal Investigator

SAKO Hiroyuki  慶應義塾大学, 医学部, 助教 (10445364)

Project Period (FY) 2010 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2010: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsGIST / c-kit / PDGFRA / Src / 胃粘膜下腫瘍 / イマチニブ / c-KIT / PDGFRα
Research Abstract

In GK7C-IR and GK22C-IR, the resistance to imatinib had been increasing from 2. 56 to 3. 73 fold comparing with the parental cells. Expression of ABC transporters : ABCC2 and ABCC5 has been shown in imatinib resistant cell lines and associated with its capacity to export a broad range of cytotoxic drugs. The status of phosphorylation of key cell signaling pathways(receptor tyrosine kinase : KIT, PDGFRa and its downstream-signaling AKT and ERK1/2 or non-receptor tyrosine kinase : SRC) was analyzed in established cell lines. As a result, the phosphorylation of SRC and ERK1/2 was increased compare to wild type cells. These results suggested that in imatinib resistant cell, the growth and survival has been to improve by high expression of ABC transporter and activation of Src and Erk1/2.

Report

(3 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • Research Products

    (3 results)

All 2011 2010

All Presentation (3 results)

  • [Presentation] GIST培養細胞の樹立とイマチニブ耐性機序の解析2011

    • Author(s)
      迫裕之
    • Organizer
      第111回日本外科学会定期学術集会
    • Place of Presentation
      (紙上開催)
    • Year and Date
      2011-05-25
    • Related Report
      2011 Annual Research Report
  • [Presentation] Establishment and characterization of imatinib mesylate-resistance gastrointestinal stromal tumor cells2010

    • Author(s)
      迫裕之
    • Organizer
      第69回日本癌学会学術総会
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2010-09-23
    • Related Report
      2011 Final Research Report
  • [Presentation] Establishment and characterization of imatinib mesylate-resistance gastrointestinal stromal tumor cells2010

    • Author(s)
      迫裕之
    • Organizer
      第69回 日本癌学会学術総会
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2010-09-23
    • Related Report
      2010 Annual Research Report

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Published: 2010-08-23   Modified: 2016-04-21  

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