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Tumor-promoting phorbol esters inhibit binding of epidermal growth factor to cellular receptors.

Tumor-promoting phorbol esters and related plant macrocyclic diterpenes inhibit the binding of epidermal growth factor to its receptors on HeLa cells. This effect shows marked structural specificity and correlates with other biological effects of these compounds on mouse skin and in cell culture systems. The active compounds inhibited binding of 125I-labeled epidermal growth factor with a 50 per-cent effective dose in the range of 10(-8) to 10(-9) M. Inhibition appears to be due to a decrease in the number of available epidermal growth factor receptors rather than a change in receptor affinity. These results suggest that certain biologic effects of tumor promoters may result from alterations in the function of cell surface receptors involved in growth regulation.