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Nuclear 24 kD fibroblast growth factor (FGF)-2 confers metastatic properties on rat bladder carcinoma cells

Oncogene volume 18, pages 6719–6724 (1999)Cite this article

Abstract

The tumorigenic and metastatic properties of rat bladder carcinoma NBT-II cells transfected with a cDNA encoding the 24 kD nuclear isoform of human fibroblast growth factor-2 (FGF-2) were analysed and compared with those cells producing the 18 kD cytoplasmic isoform FGF-2. In transfected clones, 24 kD FGF-2 was found in the nucleus, and no FGF-2 was secreted. RT – PCR analysis showed no upregulation of FGF-2-specific receptor FGFR2c expression in these proliferating transfected cells. A shorter latency period for in vivo tumor formation and abundant spontaneous lung metastases were only seen if nuclear FGF-2-producing cells were injected subcutaneously into nude mice. Intravenous injection of 24 kD FGF-2-producing cells led to extensive experimental lung metastases whereas injection of control NBT-II cells or 18 kD FGF-2-producing cells did not. As FGF-2-producing cells have no specific FGF-2 receptors, our results suggest that the 24 kD FGF-2 has nuclear targets, and activates metastatic property of carcinoma cells via a mechanism other than the conventional FGF receptor-mediated signaling pathway.

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Abbreviations

FGF:

fibroblast growth factor

FGFR:

fibroblast growth factor receptor

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Acknowledgements

We would like to thank B Bugler and H Prats for the high molecular weight 24 kD FGF-2 expression vector, Z Werb for suggestions and discussions, Y Bourgeois for nude mouse injections, D Morineau for photographs and IS Coulter for proof reading. This work was supported by the Centre National de la Recherche Scientifique and the Institut Curie, and by grants from the Association pour la Recherche sur le Cancer (ARC-4045 and a postdoctoral fellowship to M Okada-Ban), the Fondation pour la Recherche Médicale (postdoctoral fellowship to M Okada-Ban), the Ligue Nationale Française contre le Cancer (National and Paris committees) and the Groupement des Entreprises Françaises contre le Cancer (Gefluc).

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  1. UMR144 CNRS, Institut Curie, Section de recherche, 26 rue d'Ulm, 75248, Paris, Cedex 05, France

    M Okada-Ban, G Moens, J P Thiery & J Jouanneau

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  1. M Okada-Ban
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Okada-Ban, M., Moens, G., Thiery, J. et al. Nuclear 24 kD fibroblast growth factor (FGF)-2 confers metastatic properties on rat bladder carcinoma cells. Oncogene 18, 6719–6724 (1999). https://doi.org/10.1038/sj.onc.1203092

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