| Project/Area Number |
17590812
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | NHO Kinki-Chuo Chest Medical Center Clinical Research Center |
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Principal Investigator |
TAKADA Minoru NHO Kinki-Chuo Chest Medical Center Clinical Research Center, Thoracic Oncology, Director, 肺がん研究部, 部長 (20373516)
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| Co-Investigator(Kenkyū-buntansha) |
OKADA Masaji NHO Kinki-Chuo Chest Medical Center Clinical Research Center, Chief Director, 臨床研究センター, 臨床研究センター長 (40160684)
KAWAHARA Masaoki NHO Kinki-Chuo Chest Medical Center, Chief Professional Service, 統括診療部, 部長 (30344352)
SASAKI Hidefumi Nagoya City University, Medical School. Surgery II, Assistant Professor, 大学院医学研究科病態外科学腫瘍・免疫外科学, 助教 (00336695)
FUKUOKA Jyunya Toyama university hospital, Laboratory of Pathology, Assistant Professor, 附属病院病理部, 准教授 (00324575)
OKAMOTO Isamu Kinki University, School of Medicine. Medical Oncology, Assistant Professor, 医学部腫瘍内科, 講師 (10411597)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Non Small Cell Lung Cancer / Epidermal Growth Factor / tyrosine kinase inhibitor / somatic mutation / gene amplification / auto-phosphorylation / dimerization / チロシンキナーゼ阻害剤(TKIs) / 非小細胞肺癌 / EGFR / EGFR-TKIs / Gefitinib / ミスセンス変異 / インフレーム変異 / コピー数の増加 / KRAS |
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| Research Abstract |
In this study, we investigate an effect and/or the resistance mechanism of the EGFR tyrosine kinase inhibitor (TKIs) in the non small-cell lung cancer (NSCLC) using clinical specimens which have the somatic mutation in the epidermal growth factor receptor (EGFR) gene tyrosine kinase domain, and the final aim is that we find a new biological marker. By the last year, we have performed retrospective analysis about an EGFR mutation and its correlation with the clinical response using the surgical specimen of our institution.
To investigate the influence of EGFR mutation and gene amplification to cancer growth and effects of EGFR-TKIs, we have examined 16 NSCLC cell lines, including eight newly established lines from Japanese NSCLC patients. Four of the six cell lines that harbor EGFR mutations were found to be positive for EGFR amplification (delE746-A750:2lines, L858R:2lines), whereas none of the 10 cell lines negative for EGFR mutation manifested EGFR amplification, suggesting that these two types of EGFR alteration are closely associated. Endogenous EGFRs expressed in NSCLC cell lines positive for both EGFR mutation and amplification were found to be constitutively activated as a result of ligand-independent dimerization. Furthermore, the patterns of both EGFR amplification and EGFR autophosphorylation were shown to differ between cell lines harboring the two most common types of EGFR mutation (exon-19 deletion and L858R point mutation in exon 21).
These results reveal distinct biochemical properties of endogenous mutant forms of the EGFR expressed in NSCLC cell lines and may have implications for treatment of this condition.
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