Epidermal growth factor receptor pathway mitigates UVA-induced G2/M arrest in keratinocyte cells

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.