Original Paper | Published:

FGF-3 and FGF-4 elicit distinct oncogenic properties in mouse mammary myoepithelial cells

Oncogene volume 17, pages 20592071 (22 October 1998) | Download Citation

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Abstract

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 α-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.

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Affiliations

  1. Laboratory of Fundamental Virology and Immunology, Institute of Pathology, B23, University of Liège, Sart-Tilman, 4000, Liège, Belgium

    • Amin Hajitou
    •  & Claire-Michelle Calberg-Bacq
  2. Laboratory of Tumor and Developmental Biology, Institute of Pathology, B23, University of Liège, Sart-Tilman, 4000, Liège, Belgium

    • Eugenia N Baramova
    • , Kalid Bajou
    •  & Jean-Michel Foidart
  3. Laboratory of Medical Chemistry, Institute of Pathology, B23, University of Liège, Sart-Tilman, 4000, Liège, Belgium

    • Julien Collette
  4. Laboratory of Experimental Cancerology, State University of Ghent, Ghent, Belgium

    • Veerle Noë
    • , Erik Bruyneel
    •  & Marc Mareel

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Corresponding author

Correspondence to Claire-Michelle Calberg-Bacq.

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DOI

https://doi.org/10.1038/sj.onc.1202126