Animal Model Absence of Caveolin-1 Sensitizes Mouse Skin to Carcinogen-Induced Epidermal Hyperplasia and Tumor Formation

area per mouse, as compared with wild-type littermate mice. Moreover, before the development of tumors, DMBA-treatment induced severe epidermal hyperplasia in Cav-1 null mice. Both the basal cell layer and the suprabasal cell layers were expanded in treated Cav-1 null mice, as evidenced by immunostaining with cell-type specific differentiation markers (keratin-10 and keratin-14). In addition, cyclin D1 and phospho-ERK1/2 levels were up-regulated during epidermal hyperplasia , suggesting a possible mechanism for the increased susceptibility of Cav-1 null mice to tumorigenesis. However , the skin of untreated Cav-1 null mice appeared normal , without any evidence of epidermal hyperplasia , despite the fact that Cav-1 null keratinocytes failed to express caveolin-1 and showed a complete ablation of caveolae formation. Thus , Cav-1 null mice require an appropriate oncogenic stimulus , such as DMBA treatment , to reveal their increased susceptibility toward epidermal hyperplasia and skin tumor formation. Our results provide the first genetic evidence that caveolin-1 indeed functions as a tumor suppressor gene in vivo. (Am J Pathol 2003, 162:2029 –2039)