Abstract
The potent tumour promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA), and related phorbol ester tumour promoters, act by binding to specific high affinity receptors on the cell surface and this leads to changes in cell membrane structure and function, as well as highly pleiotropic effects on gene expression1–3. The ability of the phorbol ester tumour promoters4–7, and of a recently discovered tumour promoter, teleocidin8, to induce inhibition of the binding of epidermal growth factor (EGF) to its cell-surface receptors provides a convenient marker for the membrane effects of these tumour promoters. The fact that repeated applications of benzo(a)pyrene (BP) alone to mouse skin will elicit tumours suggests that it can function as both an initiator and a promoter9,10. Thus, in addition to its genotoxic effects, BP might induce membrane effects that resemble those seen with tumour promoters. Indeed, we have found that BP and certain other polycyclic aromatic hydrocarbons (PAHs) are potent inhibitors of EGF-receptor binding in the mouse embryo fibroblast cell line C3H10T½ (ref. 11). As glucocorticoids can inhibit PAH carcinogenesis12,13 and specifically inhibit tumour promotion on mouse skin14,15, we have also examined their effects on EGF receptors. We report here that glucocorticoids alone induce an increase in EGF-receptor binding in C3H10T½ cells and that pretreatment of the cells with a glucocorticoid opposes the inhibitory effects of both TPA and BP. Thus glucocorticoids may inhibit the carcinogenic process by inducing membrane effects that are reciprocal to those induced by carcinogens and tumour promoters.
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References
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Ivanovic, V., Weinstein, I. Glucocorticoids and benzo(a)pyrene have opposing effects on EGF receptor binding. Nature 293, 404–406 (1981). https://doi.org/10.1038/293404a0
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DOI: https://doi.org/10.1038/293404a0
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