PMID: 6972249Jun 1, 1981Paper

Tumor promoter-induced inhibition of epidermal growth factor binding to cultured mouse primary epidermal cells

Cancer Research
J M LockyerB E Magun

Abstract

The effect of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) and other diterpene derivatives on the binding of epidermal growth factor (EGF) to primary cultures of mouse epidermal cells was studied. 125I-EGF was used to study the specific binding of the growth factor to monolayer cultures of mouse epidermal cells grown under low-calcium culture conditions (0.06 mM Ca2+). Under these growth conditions, nonspecific binding did not exceed 10%. Initially, TPA decreased the binding of 125I-EGF to cells. However, when cells were incubated continuously in TPA plus EGF (0.25 ng/ml) for 19 hr, there was more EGF bound to the TPA-treated cells than to control cells. This phenomenon was not observed at high (5 ng/mg) EGF concentrations. Scatchard analysis of specific 125I-EGF binding at 4 degrees after a 1-hr pretreatment of the cells with TPA at 37 degrees converted a curvilinear plot to a linear plot. TPA induced a 25% decrease in the number of receptors per cell and eliminated binding of EGF to a class of high-affinity receptors. Preincubation of cells in TPA at 37 degrees for up to 13 hr followed by Scatchard analysis at 4 degrees showed that the curvilinear plot was restored and that the effects of TPA were partially r...Continue Reading

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