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  • Original Paper
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FGF1 inhibits p53-dependent apoptosis and cell cycle arrest via an intracrine pathway

Oncogene volume 24, pages 7839–7849 (2005)Cite this article

Abstract

We analysed the relationships between p53-induced apoptosis and the acidic fibroblast growth factor 1 (FGF1) survival pathway. We found that p53 activation in rat embryonic fibroblasts induced the downregulation of FGF1 expression. These data suggest that the fgf1 gene is a repressed target of p53. Unlike extracellular FGF1, which has no effect on p53-dependent pathways, intracellular FGF1 inhibits both p53-dependent apoptosis and cell growth arrest via an intracrine pathway. FGF1 increases MDM2 expression at both mRNA and protein levels. This increase is associated with an acceleration of p53 degradation, which may partly account for the ability of endogenous FGF1 to counteract p53 pathways. In the presence of FGF1, p53 was unable to transactivate bax, but no modification of p21 gene transactivation was observed. As Bax is an essential component of the p53-dependent apoptosis pathway, this suggests that intracellular FGF1 inhibits p53 pathways not only by decreasing the stability of p53, but also by modifying some of its transactivation properties. In conclusion, we showed that p53 and FGF1 pathways may interact in the cell to determine cell fate. Deregulation of one of these pathways modifies the balance between cell proliferation and cell death and may lead to tumor progression.

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Acknowledgements

We thank the Conseil Régional d'Ile-de-France, the Association pour la Recherche Contre le Cancer, the Ligue Nationale Contre le Cancer and the Fondation pour la Recherche Médicale, all of which contributed financially to the equipment used in our laboratories. Sylvina Bouleau is supported by a scholarship from the Ministère de la Jeunesse, de l'Education Nationale et de la Recherche.

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  1. Laboratoire de Génétique et Biologie Cellulaire, Université de Versailles/Saint Quentin-en Yvelines, CNRS FRE 2445, France

    Sylvina Bouleau, Hélène Grimal, Vincent Rincheval, Nelly Godefroy, Bernard Mignotte, Jean-Luc Vayssière & Flore Renaud

  2. Laboratoire de Génétique Moléculaire et Physiologique, Ecole Pratique des Hautes Etudes, 45 Avenue des Etats-Unis, Versailles Cedex, 78035, France

    Sylvina Bouleau, Hélène Grimal, Vincent Rincheval, Nelly Godefroy, Bernard Mignotte, Jean-Luc Vayssière & Flore Renaud

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  1. Sylvina Bouleau
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Correspondence to Flore Renaud.

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Bouleau, S., Grimal, H., Rincheval, V. et al. FGF1 inhibits p53-dependent apoptosis and cell cycle arrest via an intracrine pathway. Oncogene 24, 7839–7849 (2005). https://doi.org/10.1038/sj.onc.1208932

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