2011 Fiscal Year Final Research Report
Establishment and characterization for imatinib-resistant GIST cell lines from patients
| Project/Area Number |
22791302
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Digestive surgery
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| Research Institution | Keio University |
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Principal Investigator |
SAKO Hiroyuki 慶應義塾大学, 医学部, 助教 (10445364)
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| Project Period (FY) |
2010 – 2011
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| Keywords | GIST / c-kit / PDGFRA / Src |
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| 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.
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