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Localized production of TGF-β 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 vivo1. These include the induction of RNA (ref. 2), DNA (refs 3, 4) and protein synthesis5,6 during discrete phases of proliferation and differentiation7. This constitutes an ideal model for studying molecular events underlying the disruption of epidermal homeo-stasis by TPA, and its subsequent re-establishment. Transforming growth factor-β (TGF-β) can induce either growth stimulation, inhibition, or differentiation, depending on the target cell8,9. A function has been proposed for TGF-β in wound healing10 and in tumour promotion11, but the main source of TGF-β is generally thought to be platelets, macrophages or lymphocytes8, 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-β messenger RNA are induced in the epidermal cells. In situ hybridization techniques show that the main site of TGF-β synthesis is in the suprabasal differentiating epidermal cells. These results suggest that TGF-β may be a natural regulator of epidermal homeostasis which is important in tumour promotion.

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Akhurst, R., Fee, F. & Balmaint, A. Localized production of TGF-β mRNA in tumour promoter-stimulated mouse epidermis. Nature 331, 363–365 (1988). https://doi.org/10.1038/331363a0

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