Overexpression of Epidermal Growth Factor and Insulin-like Growth Factor-I Receptors and Autocrine Stimulation in Human Esophageal Carcinoma Cells

The growth-stimulatory effects of epidermal growth factor (EGF), transforming growth factor α (TGF-α), and insulin-like growth factor-I (IGF-I) on the human esophageal carcinoma cell line CE48T/VGH were evaluated. Under serum-free conditions, EGF, TGF-a, and IGF-I promoted 3.6- to 4.1-fold increased cell proliferation. Scatchard analyses and Northern blot hybridization revealed that both the EGF/TGF-a receptor and the IGF-I receptor were overexpressed in CE48T/VGH cells. Furthermore, ligand-dependent autophosphorylation of the EGF receptor and the IGF-I receptor was clearly detected using antireceptor and antiphosphotyrosine antibodies. Autocrine regulation was strongly indicated by the following evidence: (a) CE48T/VGH cells were found to express TGF-a and IGF-I genes, (b) serum-free conditioned medium promoted the growth of CE48T/VGH cells and stimulated the autophosphorylation of the EGF/TGF-a receptor and the IGF-I receptor, and (c) the addition of IGF-I receptor antibodies significantly suppressed CE48T/ VGH cell growth under serum-free conditions. Our studies suggest that the overexpression of EGF and IGF-I receptors and autocrine growth regulation may conceitedly control the proliferation of esophageal carcinoma cells.