Inhibition of ultraviolet B (UVB)-induced c-fos and c-jun expression in vivo by a tyrosine kinase inhibitor genistein.
We reported the inhibitory effects of genistein, an inhibitor of tyrosine protein kinase (TPK), on ultraviolet B (UVB)-induced expression of c-fos and c-jun in SENCAR mouse skin. UVB irradiation substantially increased transcript levels of c-fos and c-jun mRNA in mouse skin. Topical application of genistein 60 min before UVB radiation reduced c-fos and c-jun expression in the mouse skin in dose-dependent manner. Inhibition was more pronounced in skin exposed to the low dose (5 kJ/m2) than to the high dose (15 kJ/m2) of UVB radiation. In addition, genistein exhibited more inhibition of c-fos than that of c-jun. Post-application of genistein after UVB exposure down-regulated the expressions of c-fos and c-jun, but to a lesser extent compared with pre-application. A431 human epidermoid carcinoma cells, which excessively express epidermal growth factor receptors (EGF-R), were used to investigate the possible mechanism of genistein's action. The results showed that genistein down-regulated the UVB-mediated phosphorylation of TPK-dependent EGF-R in a dose-dependent manner. We concluded that inhibition of UVB-induced c-fos and c-jun expression in mouse skin by genistein may, at least in part, result from the inhibition of TPK activities and down-regulation of EGF-R phosphorylation. Suppression of UVB-induced proto-oncogene expression in mouse skin suggests that genistein may serve as a potential preventative agent against photodamage and photocarcinogenesis.
Wang
Y
Y
Department of Dermatology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Zhang
X
X
Lebwohl
M
M
DeLeo
V
V
Wei
H
H
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D004307:Dose-Response Relationship, Radiation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000528:radiation effects; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D000090063:Proto-Oncogene Mas; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics* / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D016588:Anticarcinogenic Agents; D004791:Enzyme Inhibitors; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D019833:Genistein; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases