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Differential Binding and Biological Activities of Epidermal Growth Factor and Transforming Growth Factor in a Human Pancreatic Cancer Cell Line¹

Departments of Medicine and Biological Chemistry, University of California, Irvine, California 92717

The binding characteristics and biological activities of epidermal growth factor (EGF) and transforming growth factor (TGF-) were studied in T₃M₄ human pancreatic cancer cells. Scatchard analysis of ¹²⁵I-EGF binding data at pH 7.4 indicated the presence of two orders of binding sites: a high-affinity site (K_d = 0.58 nM; 25,300 sites/cell) and a low-affinity site (K_d = 7.0 nM; 484,000 sites/cell). At pH 8.5, there was a decrease in the number of high-affinity sites. In contrast, only a single order of high-affinity sites was detected with ¹²⁵I-TGF- at either pH 7.4 (K_d = 0.57 nM; 100,200 sites/cell) or pH 8.5 (K_d = 0.70 nM; 230,400 sites/cell). The two ligands bound to the same receptor, as determined in cross-linking experiments and in competitive binding assays performed in the presence of an anti-EGF receptor antibody that allows for EGF binding. Phosphoamino acid analysis of the immunoprecipitated EGF receptor indicated that EGF exerted a greater effect than TGF- on tyrosine phosphorylation of the receptor. EGF and TGF- also exhibited different potencies with respect to their effects on inositol 1,4,5-trisphosphate generation and exerted divergent effects on the kinetics of inositol 1,4,5-trisphosphate formation. These findings point to dissimilar interactions of EGF and TGF- with the EGF receptor in T₃M₄ cells, which may lead to differential activation of signal transduction pathways by these ligands.

¹ This study was supported by Public Health Service Grant CA 40162 awarded by the National Cancer Institute (M.K.).

² To whom requests for reprints should be addressed, at Division of Endocrinology and Metabolism, Medical Sciences 1, C240, University of California, Irvine, CA 92717.

Received 6/26/91. Accepted 9/23/91.