Decreased incidence of papillomas in mice with impaired EGFR function during multi-stage skin carcinogenesis.

Genetically modified mouse lines revealed that the epidermal growth factor receptor (EGFR) is essential for the development and homoeostasis of the epidermis and hair follicles. However, more detailed studies have been precluded by the shortened lifespan of Egfr knockout mice. We employed the mouse line Wa5 (carrying a point mutation resulting in the expression of a dominant negative receptor) to analyse the impact of significantly reduced EGFR signalling during multi-stage chemical skin carcinogenesis. Seven-week-old Wa5 females and control littermates received a single application of 7,12-dimethylbenz(a)anthracene followed by multiple applications of 12-O-tetradecanoylphorbol-13-acetate for 26 weeks. Wa5 mice remained free of papillomas for a longer time and developed significantly fewer tumors than control littermates. In contrast, the mean tumor size was not different between groups. The present data indicate that EGFR signalling contributes to tumor growth during multi-stage chemical carcinogenesis of the skin in mice possibly by acting as a survival factor for skin tumor cells.