Retinoic acid-induced changes in epidermal growth factor binding and in biological responses mediated by phorbol ester tumor promoter

1984 ◽  
Vol 22 (2) ◽  
pp. 171-182 ◽  
Author(s):  
Jean M. Lockyer ◽  
G.T. Bowden ◽  
Michael A. Kelly ◽  
Mark R. Haussler ◽  
Bruce E. Magun
1982 ◽  
Vol 243 (4) ◽  
pp. E319-E324 ◽  
Author(s):  
G. Grunberger ◽  
P. Gorden

The effect of a phorbol ester tumor promoter, 12-O-tetradecanoyl phorbol-13-acetate (TPA) on 125I-insulin binding to human cells was examined. TPA markedly inhibits insulin binding to cultured human lymphocytes and macrophages but has a minimal effect on human fibroblasts. This inhibition is temperature, time, and concentration dependent. The inhibition of insulin binding to the cells at 37 degrees C occurs within minutes and diminishes by 6 h of incubation. Insulin binding is decreased by TPA whether the phorbol ester is added before, after, or simultaneously with 125I-insulin to the cell suspension. Scatchard analysis of binding to IM-9 lymphocytes indicates that TPA affects the affinity rather than the number of insulin receptors. The phorbol ester has only a small effect on 125I-human growth hormone binding in cultured human lymphocytes. TPA perturbs the insulin receptor of cultured human lymphocytes in a fashion similar to its effect on the epidermal growth factor receptor of several other cell types. The specific mechanism of TPA action that affects the receptor of these two potent growth factors (i.e., insulin and epidermal growth factor), however, is unknown.


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