Localized production of TGF-beta mRNA in tumour promoter-stimulated mouse epidermis

Abstract

Tumour promoters induce a wide spectrum of morphological and biochemical alterations when applied to mouse epidermis in vivo. These include the induction of RNA, DNA and protein synthesis during discrete phases of proliferation and differentiation. This constitutes an ideal model for studying molecular events underlying the disruption of epidermal homeostasis by TPA, and its subsequent re-establishment. Transforming growth factor-beta (TGF-beta) can induce either growth stimulation, inhibition, or differentiation, depending on the target cell. A function has been proposed for TGF-beta in wound healing and in tumour promotion, but the main source of TGF-beta is generally thought to be platelets, macrophages or lymphocytes, and a direct role for this growth factor in regulating tissue homeostasis in vivo has not been demonstrated. We show here that when the tumour promoter 12-tetradecanoyl-phorbol-13-acetate (TPA) is applied to the skin of mice, very high levels of TGF-beta messenger RNA are induced in the epidermal cells. In situ hybridization techniques show that the main site of TGF-beta synthesis is in the suprabasal differentiating epidermal cells. These results suggest that TGF-beta may be a natural regulator of epidermal homeostasis which is important in tumour promotion.