FGF-3 AND FGF-4 ELICIT DISTINCT ONCOGENIC PROPERTIES IN MOUSE MAMMARYMYOEPITHELIAL CELLS

Fibroblast Growth Factors 3 (FGF-3) and 4 (FGF-4) mere compared for th e effects they each exert on EF43 mouse cells. This non-transformed ma mmary cell line appears to be myoepithelial mainly because it expresse s cc-smooth muscle actin, The EF43 cells were infected with similar ve ctors that carry either the short fgf-3 sequence (the product of which goes into the secretory pathway), fgf-4 or the selection gene only as control, In syngeneic animals, EF43,fgf-3 cells were tumorigenic only when orthotopically implanted whereas EF43.fgf-4 cells invariably gav e rise to aggressive tumors. However, both tumor types were metastatic as evidenced by the blue micrometastases observed when the implanted cells expressed lacZ. In vitro, the FGF-3 producing cells were strongl y invasive in matrigel coated chambers whereas the EF43.fgf-4 cells on ly were invasive in type I-collagen gels, Interestingly, FGF-3 product ion greatly stimulated the synthesis of pro-MMP-9 (Matrix Metalloprote ase-9) and, to a lesser extent, that of pro-MMP-2, FGF-3 also up-regul ated the production of plasminogen activators. In contrast, FGF-4 had no effect on these secretions and the medium conditioned by the EF43.f gf-4 cells displayed the largest plasminogen activator-inhibitor activ ity, These results show that FGF-3 and FGF-4 have distinct mechanisms of action on myoepithelial cells.