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.
Jean
Christine
C
INSERM U563, CPTP, Bat B, Pavillon Lefebvre, Place du Dr. Baylac, CHU Purpan, Toulouse cedex 3, France. christine.jean@toulouse.inserm.fr
Hernandez-Pigeon
Hélène
H
Blanc
Amandine
A
Charveron
Marie
M
Laurent
Guy
G
D002455:Cell Division / Q000528:radiation effects*; D002460:Cell Line; D002470:Cell Survival / Q000528:radiation effects; D002471:Cell Transformation, Neoplastic / Q000528:radiation effects; D002478:Cells, Cultured; D000071877:Checkpoint Kinase 1; D004307:Dose-Response Relationship, Radiation; D066246:ErbB Receptors / Q000502:physiology* / Q000528:radiation effects; D016195:G2 Phase / Q000528:radiation effects*; D006801:Humans; D015603:Keratinocytes / Q000473:pathology* / Q000528:radiation effects; D020929:Mitogen-Activated Protein Kinase Kinases / Q000502:physiology; D051058:Oncogene Protein v-akt / Q000502:physiology / Q000528:radiation effects; D010766:Phosphorylation / Q000528:radiation effects; D011494:Protein Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects*
D011494:Protein Kinases; C512478:EGFR protein, human; D066246:ErbB Receptors; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1; D051058:Oncogene Protein v-akt; D020929:Mitogen-Activated Protein Kinase Kinases