The gefitinib-sensitizing mutant epidermal growth factor receptor enables transformation of a mouse fibroblast cell line.
DNA Cell Biol
; 25(4): 246-51, 2006 Apr.
Article
em En
| MEDLINE
| ID: mdl-16629597
ABSTRACT
A specific inhibitor of the Epidermal Growth Factor Receptor (EGFR), Gefitinib, displays significant antitumor effects against non-small cell lung cancers (NSCLC) that express EGFR with mutations in their tyrosine kinase domain. Although previous reports have already demonstrated that oncogenic transformation can be induced by some mutant EGFR forms, the precise differences between mutant and wild-type EGFR in terms of mechanisms of transformation have not been fully elucidated. We show here that a murine fibroblast cell line, NR6 becomes transformed by an expression level of the mutant EGFR form lacking E746-A750 that is far less than that needed with transfected wild-type EGFR. However, the mutant EGFR was unable to transform NR6 in a ligand-independent manner, as was seen with the wild-type EGFR. The consequent biological features after transformation, including DNA synthesis or cell cycle progression and biochemical characteristics such as MAPK activation mediated by the mutant EGFR are comparable and equivalent to those mediated by wild-type EGFR. These data suggest that the mutant EGFR possesses greater ligand-dependent transformation when compared with wild-type EGFR, although the exact mechanisms to account for this characteristic remain to be defined.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Quinazolinas
/
Transformação Celular Neoplásica
/
Fibroblastos
/
Receptores ErbB
/
Antineoplásicos
Limite:
Animals
Idioma:
En
Revista:
DNA Cell Biol
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Japão