A single physiologic dose of ultraviolet light exposure to human skin in vivo induces phosphorylation of epidermal growth factor receptor

Epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein of approximate 180 kDa. EGFR is involved in organ morphogenesis, maintenance a nd repair of tissues, but its signaling has also been shown to be associate d with tumor progression. Our study employing immunostaining technique in v ivo human skin demonstrated that physiologic dose of UV (4X MED) exposure t o human skin enhanced the constitutive level of EGFR by 2.5 +/- 0.5-fold at 6 and 24 h after UV exposure in comparison to normal skin but declined at 48 h time point. Basal cell layer predominantly expressed EGFR in compariso n to other cellular layers of epidermis and account for about 4.0 +/- 0.5-f old induction when compared to normal non-UV exposed skin. Constitutive EGF R staining was found all over epidermal layers in normal skin samples. In i dentical experimental conditions, UV exposure to skin induces phosphorylati on of EGFR, which has been confined to matured and differentiated layers of the epidermis. Basal cells are completely devoid of EGFR phosphorylation. UV induction of EGFR phosphorylation was found at peak level at 6 h time po int after UV exposure. At 24 h time point it remained elevated but appears diffused and declined, however EGFR phosphorylation was markedly declined a t 48 h after UV exposure. Results obtained in immunoperoxidase staining wer e also confirmed by immunoblot analysis where higher induction of EGFR phos phorylation was observed at 6 h after UV exposure, and marked reduction was found at 48 h time point. Normal skin did not show EGFR phosphorylation. E GFR and its downstream signaling have been shown to be associated with canc er progression and its metastasis, thus blocking the EGFR and its downstrea m signaling molecules can be employed as the targets for therapeutic interv ention against solar UV light induced skin cancer in human population. To o ur knowledge, this is the first in vivo human study, which clarifies the di fference in cellular localization of UV-induced constitutive and phosphoryl ated forms of EGFR in epidermal cells.