AUTOCRINE GROWTH-STIMULATION OF SW403 COLON-CARCINOMA CELL-LINE IS CAUSED BY TRANSFORMING-GROWTH-FACTOR-ALPHA-MEDIATED EPIDERMAL GROWTH-FACTOR RECEPTOR ACTIVATION

Results of recent studies indicate that some cultured human carcinoma cell lines are capable of proliferating autonomously in serum-free med ium as a result of the synthesis and secretion of transforming growth factor alpha (TGF alpha). TGF alpha interacts with epidermal growth fa ctor receptor (EGFR) and induces its activation. In an attempt to exte nd these observations, we evaluated TGF alpha-mediated autonomous grow th and constitutive EGFR activation in the human adenocarcinoma cell l ine SW403. The cell line shows synthesis of EGF receptors and TGF alph a but not EGF, and exhibits constitutive phosphorylation of the 170-kD a EGFR. Use of blocking anti-EGFR monoclonal antibodies (mAb) inhibits autonomous growth of SW403 cells and leads to a significant reduction of receptor phosphorylation. The inhibitory effect of the blocking an ti-EGFR mAb is reversible upon addition of TGF alpha. In contrast, aut onomous proliferation of SW403 cells is not inhibited by addition of n eutralizing anti-EGF mAb. Our findings suggest that the proliferation of cells of the human SW403 adenocarcinoma cell line is regulated by a n autocrine TGF alpha loop and that this regulatory pathway can be int errupted by using anti-EGFR mAb.