Effects of 12-O-tetradecanoyl phorbol-13-acetate and epidermal growth factor on the proliferation of human mutant fibroblasts in vitro.

Cultures of skin fibroblasts (SF) from individuals with hereditary adenomatosis of the colon and rectum (ACR) and from normal individuals were exposed to 12-O-tetradecanoyl phorbol-13-acetate (TPA) (0.5-100 ng/ml), and epidermal growth factor (EGF) (0.01-10.0 ng/ml) at both low and high cell densities. Cell proliferation of low density cultures (4.75 x 10(3) cells/cm2) was inhibited by TPA, while cell proliferation of high density cultures (6 x 10(4) cells/cm2) was stimulated by TPA. EGF was mitogenic at both cell densities of normal and ACR-SF cultures. TPA and EGF each produced characteristic changes in the morphology of ACR-SF colonies. These results suggest that EGF and TPA may share only 1 class of receptors, and that TPA may be used to monitor cancer progression.