Inhibition of ultraviolet B (UVB)-induced c-fos and c-jun expression in vivo by a tyrosine kinase inhibitor genistein

• Published in: Carcinogenesis (New York) 1998-04, Vol.19 (4), p.649-654
• Main Authors: YAN WANG, YAPING E, XUESHU ZHANG, LEBWOHL, M, DELEO, V, HUACHEN WEI
• Format: Article
• Language: English
• Subjects: Animals; Anticarcinogenic Agents - pharmacology; Biological and medical sciences; Dose-Response Relationship, Radiation; Enzyme Inhibitors - pharmacology; ErbB Receptors - metabolism; Female; Gene Expression Regulation - drug effects; Gene Expression Regulation - radiation effects; General pharmacology; Genistein - pharmacology; Humans; Medical sciences; Mice; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Phosphorylation; Protein-Tyrosine Kinases - antagonists & inhibitors; Proto-Oncogene Proteins c-fos - genetics; Proto-Oncogene Proteins c-fos - metabolism; Proto-Oncogene Proteins c-jun - genetics; Proto-Oncogene Proteins c-jun - metabolism; Tumor Cells, Cultured
• ISSN: 0143-3334; 1460-2180; 1460-2180
• DOI: 10.1093/carcin/19.4.649

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.