Biological analysis of the single codon deletion in Exon 19 of EGF receptor in non-small cell lung cancer responsive to gefitinib
H. Nitanai, M. Ogasawara, K. Yamauchi, N. Sasaki, Y. Utsumi, N. Suzuki, S. Akiyama, H. Nagashima, Y. Nakamura, H. Kobayashi, H. Inoue (Morioka, Toon, Japan)
Source: Annual Congress 2009 - Epidemiology and management of lung cancer
Session: Epidemiology and management of lung cancer
Session type: E-Communication Session
Number: 4692
Disease area: Thoracic oncology
Abstract Introduction: The in-frame 15-bp deletional mutation (delE746–A750 type deletion) in EGFR (epidermal growth factor receptor) is one of the common mutation of lung cancer sensitive to tyrosine kinase inhibitors (TKI). However, a responsible codon in this type of mutation remains unclear. We have recently found the case of a 67 year old Japanese woman with lung cancer which contained the unique single codon deletion (746) in Exon 19 of EGFR responsive to gefitinib. In this paper, we analyzed a relationship between this single codon deletion and EGFR activation by introducing the mutated EGFR gene to L929 cells. Methods: The expression plasmid vector of wild type EGFR and the single codon deletion mutant EGFR at codon 746 containing an HA tag was constructed. Plasmids were transiently transfected into L929 cells and transfectants were designated L929-pEGFR and L929-pDel cells, respectively. These cells were stimulated with EGF (100ng/ml) and lysed for immunoblot analysis with antibodies against phosphor-tyrosine. Results: Under unstimulated conditions, deletion mutant EGFR was highly phosphorylated. On the other hand, autophosphorylation of wild-type EGFR was barely detectable. The wild type EGFR were phosphorylated to a greater extent for a 2 min EGF stimulation. The phosphorylation of deletion mutant EGFR was reduced by the addition of EGF in L929 pDel cells. Conclusion: Deletion mutant EGFR was autophosphorylated without EGF, thus suggesting that the single codon (746) deletion mutant may be associated with the countinuous activation of EGFR. The dephosphorylation of mutant EGFR with EGF may have some relationship in regards to its sensitivity to TKI.
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H. Nitanai, M. Ogasawara, K. Yamauchi, N. Sasaki, Y. Utsumi, N. Suzuki, S. Akiyama, H. Nagashima, Y. Nakamura, H. Kobayashi, H. Inoue (Morioka, Toon, Japan). Biological analysis of the single codon deletion in Exon 19 of EGF receptor in non-small cell lung cancer responsive to gefitinib. Eur Respir J 2009; 34: Suppl. 53, 4692
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