Figure 1. Ras activity and epidermal proliferation. Genetic elimination of H-Ras, N-Ras and K-Ras from epidermis (Ras KO) causes a defective epidermis characterized by low levels of expression of c-Myc and ΔNp63 and high expression levels of p21^Cip1 and p15^INK4b in the basal layer. In contrast, normal epidermis (wild-type Ras) expresses high levels of c-Myc and ΔNp63 in the basal but not in the suprabasal layer. An opposite pattern of expression is shown by p21^Cip1 and p15^INK4b which are highly expressed in the suprabasal layer but not in the basal layer. In most scenarios, expression of endogenous oncogenic H-Ras and K-Ras mutants in the epidermis do not affect epidermal development. However, when oncogenic Ras mutants are expressed at unphysiologically elevated levels in transgenic mice, they efficiently induce papillomas and squamous cell carcinomas. See text for details.