FGF-3 and FGF-4 elicit distinct oncogenic properties in mouse mammary myoepithelial cells.
Fibroblast Growth Factors 3 (FGF-3) and 4 (FGF-4) were compared for the effects they each exert on EF43 mouse cells. This non-transformed mammary cell line appears to be myoepithelial mainly because it expresses alpha-smooth muscle actin. The EF43 cells were infected with similar vectors 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 gave 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 strongly invasive in matrigel coated chambers whereas the EF43.fgf-4 cells only were invasive in type I-collagen gels. Interestingly, FGF-3 production greatly stimulated the synthesis of pro-MMP-9 (Matrix Metalloprotease-9) and, to a lesser extent, that of pro-MMP-2. FGF-3 also up-regulated the production of plasminogen activators. In contrast, FGF-4 had no effect on these secretions and the medium conditioned by the EF43.fgf-4 cells displayed the largest plasminogen activator-inhibitor activity. These results show that FGF-3 and FGF-4 have distinct mechanisms of action on myoepithelial cells.
Hajitou
A
A
Laboratory of Fundamental Virology and Immunology, Institute of Pathology, University of Liège, Belgium.
Baramova
E N
EN
Bajou
K
K
Noë
V
V
Bruyneel
E
E
Mareel
M
M
Collette
J
J
Foidart
J M
JM
Calberg-Bacq
C M
CM
D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D017364:Collagenases / Q000378:metabolism; D004847:Epithelial Cells; D005260:Female; D051518:Fibroblast Growth Factor 3; D051519:Fibroblast Growth Factor 4; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000502:physiology*; D018093:Gelatinases / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000473:pathology*; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D015849:Plasminogen Inactivators / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
C489197:Fgf3 protein, mouse; C496446:Fgf4 protein, mouse; D051518:Fibroblast Growth Factor 3; D051519:Fibroblast Growth Factor 4; D015849:Plasminogen Inactivators; D011518:Proto-Oncogene Proteins; D005346:Fibroblast Growth Factors; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9