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 and repair of tissues, but its signaling has also been shown to be associated with tumor progression. Our study employing immunostaining technique in vivo human skin demonstrated that physiologic dose of UV (4X MED) exposure to 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 comparison to other cellular layers of epidermis and account for about 4.0+/-0.5-fold induction when compared to normal non-UV exposed skin. Constitutive EGFR staining was found all over epidermal layers in normal skin samples. In identical experimental conditions, UV exposure to skin induces phosphorylation 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 point after UV exposure. At 24 h time point it remained elevated but appears diffused and declined, however EGFR phosphorylation was markedly declined at 48 h after UV exposure. Results obtained in immunoperoxidase staining were also confirmed by immunoblot analysis where higher induction of EGFR phosphorylation 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. EGFR and its downstream signaling have been shown to be associated with cancer progression and its metastasis, thus blocking the EGFR and its downstream signaling molecules can be employed as the targets for therapeutic intervention against solar UV light induced skin cancer in human population. To our knowledge, this is the first in vivo human study, which clarifies the difference in cellular localization of UV-induced constitutive and phosphorylated forms of EGFR in epidermal cells.
Katiyar
S K
SK
Department of Dermatology, School of Medicine, Case Western Reserve University, Cleveland, OH, USA. skatiyar@uab.edu
D066246:ErbB Receptors / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000528:radiation effects; D015151:Immunoblotting; D007124:Immunoenzyme Techniques; D010766:Phosphorylation; D015398:Signal Transduction / Q000528:radiation effects*; D012867:Skin / Q000378:metabolism / Q000528:radiation effects*; D014466:Ultraviolet Rays
D066246:ErbB Receptors