Activation of epidermal growth factor receptor and its downstream signaling pathway by nitric oxide in response to ionizing radiation.
Mol Cancer Res
; 6(6): 996-1002, 2008 Jun.
Article
em En
| MEDLINE
| ID: mdl-18567803
ABSTRACT
Epidermal growth factor receptor (EGFR) is activated by ionizing radiation (IR), but the molecular mechanism for this effect is unknown. We have found that intracellular generation of nitric oxide (NO) by NO synthase (NOS) is required for the rapid activation of EGFR phosphorylation by IR. Treatment of A549 lung cancer cells with IR increased NOS activity within minutes, accompanied by an increase of NO. 2-Phenyl-4,4,5,5,-tetramethylimidazolline-1-oxyl-3-oxide, an NO scavenger, and NG-monomethyl-l-arginine, an NOS inhibitor, abolished the increase in intracellular NO and activation of EGFR by IR. In addition, an NO donor alone induced EGFR phosphorylation. Transient transfection with small interfering RNA for endothelial NOS reduced IR-induced NO production and suppressed IR-induced EGFR activation. Overexpression of endothelial NOS increased IR-induced NO generation and EGFR activation. These results indicate a novel molecular mechanism for EGFR activation by IR-induced NO production via NOS.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Radiação Ionizante
/
Receptores ErbB
/
Óxido Nítrico
Limite:
Humans
Idioma:
En
Revista:
Mol Cancer Res
Ano de publicação:
2008
Tipo de documento:
Article