Membrane-mediated responses to 12-O-tetradecanoylphorbol-13-acetate in human skin fibroblasts.

The effects on primary human skin fibroblasts of the structurally unrelated tumour promoters 12-O-tetradecanoylphorbol-13-acetate (TPA) and teleocidin B were compared with those of epidermal growth factor and the non-promoting derivative 4-O-methyl TPA by means of two-dimensional gel electrophoresis. Both TPA and teleocidin B caused a marked increase in the synthesis of two polypeptides of molecular weights 44 kilodaltons (P44) and 55 kilodaltons (P55). P55 was complexed in cell lysates by antiactin antibody and was shown to be a component of the cytoskeleton. P44 migrated very near to actin, but it was shown not to be a variant form of actin. No such specific increase in polypeptide synthesis was observed following treatment with either epidermal growth factor or 4-O-methyl TPA. TPA inhibited the beta-adrenergic hormone response in the same human skin fibroblasts.