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RhoB controls the 24 kDa FGF-2-induced radioresistance in HeLa cells by preventing post-mitotic cell death

Oncogene volume 21, pages 5998–6006 (2002)Cite this article

Abstract

Farnesylated Ras oncoprotein induces a cellular resistance to ionizing radiation that can be reversed by farnesyltransferase inhibitors (FTI). We previously demonstrated that, expression of the 24 kDa FGF2 isoform in wild type ras bearing HeLa cells, induced radioresistance which was also reversed by FTI. We tested the hypothesis that wild type Ras or RhoB, which has been proposed as a potential FTI target, could control the FGF-2-induced radioresistance mechanisms. For this, we expressed inducible dominant negative forms of Ras (RasN17) and Rho (RhoBN19) in 24 kDa FGF2 transfected HeLa cells and analysed their survival after irradiation. While no cell survival modification was observed after RasN17 induction, the expression of RhoBN19 induced a radiosensitization of FGF2 radioresistant HeLa cells in the same range as the one observed after a 48 h treatment with the specific FTI, R115777. Moreover, we showed that activated RhoB but not RhoA induced radioresistance in NIH3T3 cells. The radiosensitizer effect of RhoBN19 expression was due to the induction of the radiation induced post-mitotic cell death. Taken together, these data demonstrate that 24 kDa FGF-2-induced radioresistance is controlled by Rho pathways and suggest that RhoB should be a major determinant in cellular resistance to ionizing radiation.

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Acknowledgements

We thank Dr John White for providing us pGRE5.2 plasmid and Dr Dave End of Janssen Research company for providing the R115777 inhibitor. This work has been supported by the Ministere de la Recherche et de l'Enseignement Supérieur (I Ader, G Favre), by the Groupe de Recherche de l'Institut Claudius Regaud (C Toulas, G Favre) and by Electricité de France.

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Authors and Affiliations

  1. Département d'Innovation thérapeutique et Oncologie Moléculaire, Oncologie Cellulaire et Moléculaire, INSERM U563, Centre de Lutte Contre le Cancer Claudius Regaud, 20-24 rue du Pont St Pierre, Toulouse Cedex, 31052, France

    Isabelle Ader, Christine Toulas, Florence Dalenc, Caroline Delmas, Elizabeth Cohen-Jonathan & Gilles Favre

  2. Département de Radiothérapie, Centre de Lutte Contre le Cancer Claudius Regaud, 20-24 rue du Pont St Pierre, Toulouse Cedex, 31052, France

    Jacques Bonnet & Elizabeth Cohen-Jonathan

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  1. Isabelle Ader
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  2. Christine Toulas
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  7. Gilles Favre
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Correspondence to Gilles Favre.

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Ader, I., Toulas, C., Dalenc, F. et al. RhoB controls the 24 kDa FGF-2-induced radioresistance in HeLa cells by preventing post-mitotic cell death. Oncogene 21, 5998–6006 (2002). https://doi.org/10.1038/sj.onc.1205746

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