MDA-MB-134 BREAST-CARCINOMA CELLS OVEREXPRESS FIBROBLAST GROWTH-FACTOR (FGF) RECEPTORS AND ARE GROWTH-INHIBITED BY FGF LIGANDS

Overexpression of some transmembrane tyrosine kinase growth factor rec eptors in breast and other tumors has been found to correlate with poo r prognosis. Following the cloning of the first two members of the fib roblast growth factor family of receptors (FGFRs), amplification of th ese receptors in breast carcinomas was found. We have examined 23 brea st carcinoma cell lines to determine the extent of expression of mRNA for fgfrs 1 through 4. All breast carcinoma cell lines examined expres sed mRNA for at least one fgfr and several expressed high mRNA levels for a particular receptor. MDA-MB-134, an estrogen receptor-positive c ell line, expressed very high levels of mRNA for fgfr-1 and elevated l evels of mRNA for fgfr-4. This cell line was found to have an amplifie d fgfr-1 gene, but the gene for fgfr-4 was not amplified. MDA-MB-453 c ells were found to express high levels of mRNA for fgfr-4 without ampl ification of the gene. MDA-MB- 134 cells were examined for their respo nse to FGF ligands. Tyrosine phosphorylation of a M(r) 150,000 protein resulted when MDA-MB-134 cells were treated with FGF-1 or FGF-2, impl ying the presence of a functional FGFR-1. MDA-MB-134 cells were growth -inhibited by picomolar concentrations of FGF-1 or FGF-2 in a dose-dep endent manner under both anchorage-independent and anchorage-dependent conditions. These results may provide insight into the consequences o f FGFR overexpression in breast tumors and the development of treatmen t modalities which use manipulation of growth factor responses.