Follicular origin of epidermal papillomas in v-Ha-ras transgenic TG.AC mouse skin.

A follicular origin for some skin tumors has been hypothesized in both humans and animal models. Because of its rapid and sensitive response to tumor promoter treatment, a v-Ha-ras transgenic (TG.AC) mouse line was used to determine the origins of epidermal papillomas. Using histological studies and transgene expression as a marker for papilloma development, we determined that pedunculated papillomas arose from focal hyperplasias of the permanent portion of the follicular epithelium in phorbol 12-myristate 13-acetate-treated TG.AC mouse skin. Damage to the hair follicle by depilation was also sufficient to induce papillomas that were histologically indistinguishable from those produced by chemical exposure. Identification of the cellular origins of papillomas in this transgenic mouse model will allow for an analysis of the role of the hair follicle and hair cycle-associated signaling in tumor development.