ROLE OF EPIDERMAL-GROWTH-FACTOR RECEPTOR IN TUMOR PROGRESSION IN TRANSFORMED HUMAN MAMMARY EPITHELIAL-CELLS

The presence of epidermal-growth-factor receptors (EGFR) and of its li gands (TGF alpha: and amphiregulin) in breast-cancer tissues suggests that they play a paracrine/autocrine role in tumor growth or progressi on. This hypothesis was tested on 3 cell lines, S2T2, NS2T2A and NS2T2 A1. These epithelial cells are derived from a normal human breast-epit helial-cell culture transformed by SV40-T Ag, are of the same clonal o rigin, have respectively increasing levels of EGFR, TGF alpha, amphire gulin and of thymidine-kinase activity associated with increasing tumo rigenic potential in nude mice (tumor intake and tumor volume). The mo noclonal antibody MAb 425, which blocks ligands interaction with EGFR, reduced by more than 90% anchorage-independent growth of the most tum origenic cells, NS2T2A I. Another anti-EGFR MAb, 528, reduced to 25% o f controls the mean tumor mass after NS2T2A1 grafting in mice. Anti-se nse RNA expression of EGFR in these cells confirmed the importance of this receptor in tumor progression, since it reduced significantly the tumor volume and tumor weight of NS2T2A1 cells to 16% of those in moc k-transfected control cells. (C) 1998 Wiley-Liss, Inc.