FGF Ligands Growth Factor (FGF) Receptors and Are Growth-inhibited by MDA-MB-134 Breast Carcinoma Cells Overexpress Fibroblast

Overexpression of some transmembrane tyrosine kinase growth factor receptors in breast and other tumors has been found to correlate with poor prognosis. Following the cloning of the first two members of the fibroblast growth factor family of receptors (FGFRs), amplification of these receptors in breast carcinomas was found. We have examined 23 breast carcinoma cell lines to determine the extent of expression of mRNA for fgfrs 1 through 4. All breast carcinoma cell lines examined expressed mRNA for at least one fgfr and several expressed high mRNA levels for a particular receptor. MDA-MB-134, an estrogen receptor-positive cell line, expressed very high levels of mRNA forfgfr-1 and elevated levels of mRNA forfgh'-4. This cell line was found to have an amplified fgfr-I gene, but the gene for fgfr-4 was not amplified. MDA-MB-453 cells were found to express high levels of mRNA forfgfr-4 without amplification of the gene. MDA-MB-134 cells were examined for their response to FGF ligands. Tyrosine phosphorylation of a Mr 150,000 protein resulted when MDA-MB-134 cells were treated with FGF-1 or FGF-2, implying 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-dependent manner under both anchorage-independent and anchorage-dependent conditions. These results may provide insight into the consequences of FGFR overexpression in breast tumors and the development of treatment modalities which use manipulation of growth factor responses.