ALTERATIONS IN GROWTH-FACTOR PATHWAYS IN MULTISTAGE CARCINOGENESIS OF TRACHEAL EPITHELIAL-CELLS

The role of peptide growth factors in the process of multistage carcinogenesis of rat tracheal epithelial (RTE) cells was assessed by examining growth factor requirements and expression of growth factors and their receptors in normal and transformed RTE cells. Transformed RTE cell lines show decreased requirements for bovine pituitary extract, insulin and epidermal growth factor compared to primary RTE cells in culture. An autocrine role for TGF-alpha in transformed RTE cells is suggested by data showing TGF-alpha production and decreased proliferation in the presence of TGF-alpha antisera and TGF-alpha/EGF receptor kinase inhibitor. Therefore, decreased EGF requirements in transformed RTE cells could be explained by autocrine TGF-alpha regulation. In contrast, no evidence for an insulin/IGF-I autocrine pathway could be detected in transformed RTE cells. These data indicate that multiple alterations in growth factor pathways occur in transformed RTE cells.