Epidermal growth factor receptor pathway mitigates UVA-induced G2/M arrest in keratinocyte cells.
J Invest Dermatol
; 127(10): 2418-24, 2007 Oct.
Article
em En
| MEDLINE
| ID: mdl-17495959
ABSTRACT
UVA irradiation contributes largely to photocarcinogenesis. In the process of keratinocyte transformation, the activation of EGFR by UV is now considered as a critical event. However, the mechanism that links the EGFR pathway and photocarcinogenesis is not totally understood. In this study, we report that the EGFR/Akt pathway mitigated G2/M arrest in human HaCaT keratinocytes and normal human keratinocytes treated with low doses of UVA irradiation. EGFR-mediated Akt activation resulted in increased level of checkpoint 1 kinase (Chk1) inhibitory phosphorylation (Ser280). In contrast, EGFR/Akt pathway inhibition resulted in the abrogation of Ser280 Chk1 phosphorylation, increased level of Chk1 stimulatory phosphorylation (Ser345), and restoration of G2/M arrest. Altogether, these results suggest that, after UVA exposure, the EGFR/Akt pathway subverts the G2/M checkpoint. This effect may have serious implications in photocarcinogenesis by allowing damaged cells to transit through the cell cycle.
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Base de dados:
MEDLINE
Assunto principal:
Raios Ultravioleta
/
Queratinócitos
/
Divisão Celular
/
Fase G2
/
Receptores ErbB
Limite:
Humans
Idioma:
En
Revista:
J Invest Dermatol
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
França