Transforming growth factor-beta expression in fibropapillomas induced by bovine papillomavirus type 1, in normal bovine skin, and in BPV-1-transformed cells.

There is substantial evidence to suggest that transforming growth factor-beta (TGF-beta) plays an important role in wound healing and tissue repair as well as in carcinogenesis. It has also been observed that naturally occurring bovine papillomavirus type 1 (BPV-1)-induced bovine fibropapillomas occur predominantly at traumatized sites of the body, suggesting that humoral factors released in wounds might be important for papillomavirus infection. We have therefore investigated the possible role of TGF-beta 1 in BPV-1 infections. Two antipeptide antibodies which recognize different epitopes in the N-terminus of TGF-beta 1 were used to localize TGF-beta 1 in bovine fibropapillomas and normal bovine skin using immunohistochemical methods. Staining by anti-LC(1-30) is intracellular in suprabasal keratinocytes of the epidermis as well as the hair follicles and sebaceous glands and correlates with known sites of TGF-beta 1 mRNA synthesis. Anti-CC(1-30) staining is extracellular in the immediately underlying dermis. Neither the pattern nor intensity of TGF-beta 1 staining was affected by BPV-1 infection. C127 cells and BPV-1-transformed C127 cells were compared for TGF-beta 1 mRNA expression and secretion of TGF-beta 1 peptide. Although the levels of messenger RNA and secreted TGF-beta 1 peptide were similar in both cell types, five- to six-fold greater amounts of TGF-beta-like activity per cell was detected in media conditioned by the uninfected cells. TGF-beta 1 treatment had no effect on the growth rate of either cell type or on BPV-1 gene expression in the transformed cells.