Tumoral progression of human breast epithelial cells secreting FGF2 and FGF4

The human breast epithelial cell line HBL100 synthesizes and secretes FGF2, is able to grow in soft agar but is not tumorigenic in nude mice. Transfection of this cell line with the FGF4 gene led to its tumorigenic conversion in a dose-dependent manner as assessed by growth under serum-free conditions, growth in soft agar and growth as xenografts in nude mice. Clones of FGF4-transfected cells producing different amounts of FGF4 secreted similar quantities of FGF2. Exogenously added recombinant FGF4 stimulated growth of clones that do not express this growth factor, but did not affect growth of FGF4-producers. Neutralizing IgGs directed against FGF2 strongly inhibited growth of clones that do not produce FGF4, but did not affect growth of FGF4-producers, indicating that the latter are FGF2-independent. Cross-linking experiments done with 125I-FGF2 showed a down-regulation of FGF receptors from the cell surface of FGF4-expressing clones. Taken together, these results indicate that the FGF signalling pathway may be involved during tumoral progression of human breast epithelial cells and that there is a dose-dependent relationship between the quantity of FGF4 produced and tumor development.