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Functional Rac-1 and Nck signaling networks are required for FGF-2-induced DNA synthesis in MCF-7 cells

Oncogene volume 18, pages 6425–6433 (1999)Cite this article

Abstract

The effects of Fibroblast Growth Factor-2 (FGF-2) on breast cancer cell DNA synthesis are controversial. To elucidate the mechanisms by which FGF-2 stimulates or inhibits DNA synthesis, we analysed FGF-2 signaling pathways in breast cancer MCF-7 and MCF-7 cells overexpressing Ha-Ras (MCF-7ras). We found that FGF-2-induction of DNA synthesis correlates with Ras transient activation, FRS-2 tyrosine phosphorylation and low level of expression of p66Shc. In addition, Nck-associated proteins are highly tyrosine phosphorylated and JNK reaches a higher level of activation when FGF-2 triggers DNA synthesis. Interestingly upon FGF-2 treatment, JNK activation and DNA synthesis are dependent on Rac-1 activity. These results confirm that in MCF-7 cells, induction of DNA synthesis by FGF-2 requires a transient activation of the Ras/MAPK cascade and demonstrates for the first time that intact Rac-1 and Nck signaling networks are required.

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Acknowledgements

The authors gratefully acknowledge Dr JJM Bergeron for his constant support during the course of this work, Dr MD Katinka for helpful suggestions, PH Cameron, Drs N Lamarche and S Palcy for comments on the manuscript. J-F Liu was funded by a fellowship from the Ligue Contre le Cancer and E Chevet was supported by a post-doctoral fellowship from the `Association pour la Recherche contre le Cancer'. This work was funded in part by grants from the Ministère de l'Education Nationale to D Barritault and from the Medical Research Council of Canada to L Larose.

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Authors and Affiliations

  1. Department of Anatomy and Cell Biology, McGill University, 3640 University Street, Montreal, QC, H3A 2B2, Canada

    Eric Chevet

  2. Department of Experimental Medicine, McGill University 3640 University Street, Montreal, QC, H3A 2B2, Canada

    Sem Kebache & Louise Larose

  3. Laboratoire de Recherche Oncologie Moléculaire Humaine (EA 445), UFR Léonard de Vinci, Université Paris-nord, 74, rue Marcel Cachin, 93012,, Bobigny, France

    Jiang-Feng Liu & Michel Crépin

  4. Laboratoire CRRET, Université Paris-XII, 61 Avenue du Général De Gaulle, 94010, Créteil Cédex, France

    Jiang-Feng Liu, Gilles Lemaitre & Denis Barritault

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Liu, JF., Chevet, E., Kebache, S. et al. Functional Rac-1 and Nck signaling networks are required for FGF-2-induced DNA synthesis in MCF-7 cells. Oncogene 18, 6425–6433 (1999). https://doi.org/10.1038/sj.onc.1203027

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