Transforming Growth Factor fa Induction Is Associated with Transforming Growth Factors fa and fa Down-Modulation in 12-0-Tetradecanoylphorbol-13-acetate-induced Skin Hyperplasia

Acute treatment of mouse skin with the tumor promoter 12-O-tetra-decanoylphorbol-13-acetate (TPA) induces marked epidermal hyperplasia, which is well evident by 24 h and maximal by 48-72 h. These effects are associated with the early induction of transforming growth factor (TGF) Pi expression in the epidermis. We show here that, in contrast to TGF-β1, TGF-β2, and TGF-β3, skin expression is significantly down-modulated in response to TPA TGF-fe RNA levels decreased by 6 h of treatment but returned to normal or even higher levels at later times. The TGF-β3 protein could be detected immunohistochemically in both dermis and epidermis in control skins and at early times of TPA treatment However, at later times, TGF-β3 was found only in dermal cells and not in the epidermis. TGF-β2 RNA expression was found to be significantly down-modulated by 24 h of TPA treatment and remained low even at later times. Thus, differential control of the 3 TGF-β isoforms appears to be a likely determinant of normal skin homeostasis and could be at least partially responsible for TPA-induced skin hyperplasia. © 1993, American Association for Cancer Research. All rights reserved.