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Retinoic acid and arsenic trioxide cooperate for apoptosis through phosphorylated RXR alpha

Oncogene volume 24, pages 2277–2288 (2005)Cite this article

Abstract

Arsenite trioxide (As2O3) induces apoptosis in several cell lines by disturbing key signal transduction pathways through its oxidative properties. Here, we report that As2O3 also induces the phosphorylation of the retinoid receptor RXRα, subsequent to oxidative damages and the activation of the stress-activated protein kinases cascade (JNKs). We also report that RA amplifies both As2O3-induced phosphorylation of RXRα and apoptosis. Taking advantage of ‘rescue’ F9 cell lines expressing RXRα mutated at its phosphorylation sites, in an RXRα null background, we provide evidence that RXRα is a key element involved in that potentiating effect. Finally, we demonstrate that As2O3 also abrogates the transactivation of RA-target genes.

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Acknowledgements

We thank S Adam-Stitah, J Clifford, D Metzger and P Chambon for providing mutant F9 cell lines. We are grateful to Dr Theodosiou for the generous gift of the M3/M6 expression vector. We are grateful to Gaetan Bour for critically reading the manuscript. We thank JL Plassat for helpful advice on quantitative RT–PCR. We also thank members of the cell culture and oligonucleotides facilities for help. This work was supported by funds from the Centre National de la Recherche scientifique (CNRS), the Institut National de la Recherche Médicale (INSERM), the Hôpital Universitaire de Strasbourg, the Association pour la Recherche sur le Cancer and Bristol-Myers Squibb. Anne Tarrade was supported by the ‘Ligue Nationale contre le Cancer’. JB was supported by the Ministère de la Recherche et de l'Enseignement Supérieur, by the ‘Ligue Nationale contre le Cancer’ and by the ‘Fondation pour la Recherche Médicale’.

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Author notes

  1. Anne Tarrade

    Present address: Laboratoire de Neurogénétique Moléculaire, INSERM E.0223, Génopole, 2 rue Gaston Crémieux, 91057, Evry Cedex, France

  2. Julie Bastien

    Present address: Cancer Research UK, Signal Transduction Laboratory, 44 Lincoln's Inn Field, London, WC2A3PX, UK

Authors and Affiliations

  1. Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, BP 10142, 67404, Illkirch Cedex, France

    Anne Tarrade, Julie Bastien, Nathalie Bruck, Annie Bauer & Cécile Rochette-Egly

  2. Laboratorio di Biologia Molecolare, Istituto di Ricerche Farmacologiche Mario Negri, Via Eritrea 62, 20157, Milano, Italy

    Maurizio Gianni

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Correspondence to Cécile Rochette-Egly.

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Tarrade, A., Bastien, J., Bruck, N. et al. Retinoic acid and arsenic trioxide cooperate for apoptosis through phosphorylated RXR alpha. Oncogene 24, 2277–2288 (2005). https://doi.org/10.1038/sj.onc.1208402

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