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Functional characterization of ATAD2 as a new cancer/testis factor and a predictor of poor prognosis in breast and lung cancers

Oncogene volume 29, pages 5171–5181 (2010)Cite this article

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Abstract

Cancer cells frequently express genes normally active in male germ cells. ATAD2 is one of them encoding a conserved factor harbouring an AAA type ATPase domain and a bromodomain. We show here that ATAD2 is highly expressed in testis as well as in many cancers of different origins and that its high expression is a strong predictor of rapid mortality in lung and breast cancers. These observations suggest that ATAD2 acts on upstream and basic cellular processes to enhance oncogenesis in a variety of unrelated cell types. Accordingly, our functional studies show that ATAD2 controls chromatin dynamics, genome transcriptional activities and apoptotic cell response. We could also highlight some of the important intrinsic properties of its two regulatory domains, including a functional cross-talk between the AAA ATPase domain and the bromodomain. Altogether, these data indicate that ATAD2 overexpression in somatic cells, by acting on basic properties of chromatin, may contribute to malignant transformation.

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Acknowledgements

This work was supported by the ‘ANR blanc-Episperm’, INCa-DHOS’ and ‘ARC-ARECA’ research programs. CL and SM are supported by the PhD fellowship program of Région Rhône-Alpes and the post-doc fellowship program of INCa (AO 2006), respectively. AD salary is paid by the INCa–DHOS funds. Transcriptomic analyses of lung cancer patients were obtained thanks to the Ligue Contre le Cancer ‘Carte d’identité des Tumeurs’ (CIT) program. We acknowledge the support of the Nice-Sophia Antipolis Transcriptome Platform of the Marseille–Nice Genopole, in which the microarray experiments were carried out. Special thanks are due to Géraldine Rios for microarray production. We also acknowledge the support of the microscopy platform, Albert Bonniot Institute, Grenoble, and thank Catherine Souchier for her precious help in the FRAP experiments.

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Authors and Affiliations

  1. INSERM, U823; Université Joseph Fourier—Grenoble 1; Institut Albert Bonniot, Grenoble, France

    C Caron, C Lestrat, S Marsal, E Escoffier, S Curtet, A Debernardi, C Brambilla, E Brambilla, S Rousseaux & S Khochbin

  2. CNRS and Université de Nice Sophia Antipolis, Institut de Pharmacologie Moléculaire et Cellulaire, Sophia Antipolis, France

    V Virolle & P Barbry

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  1. C Caron
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  2. C Lestrat
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Correspondence to C Caron or S Khochbin.

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Caron, C., Lestrat, C., Marsal, S. et al. Functional characterization of ATAD2 as a new cancer/testis factor and a predictor of poor prognosis in breast and lung cancers. Oncogene 29, 5171–5181 (2010). https://doi.org/10.1038/onc.2010.259

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