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The methyl-CpG-binding protein MECP2 is required for prostate cancer cell growth

Oncogene volume 25, pages 1358–1366 (2006)Cite this article

Abstract

The incidence of prostate cancer is increasing in western countries because of population aging. Prostate cancer begins as an androgen-dependent disease, but it can become androgen independent at a later stage or in tumors recurring after an antihormonal treatment. Although many genetic events have been described to be involved in androgen-dependent and/or -independent prostate cancer growth, little is known about the contribution of epigenetic events. Here we have examined the possibility that the methyl-CpG-binding protein MECP2 might play a role in controlling the growth of prostate cancer cells. Inhibition of MECP2 expression by stable short hairpin RNA stopped the growth of both normal and cancer human prostate cells. In addition, ectopic expression of the MECP2 conferred a growth advantage to human prostate cancer cells. More importantly, this expression allowed androgen-dependent cells to grow independently of androgen stimulation and to retain tumorigenic properties in androgen-depleted conditions. Analysis of signaling pathways showed that this effect is independent of androgen receptor signaling. Instead, MECP2 appears to act by maintaining a constant c-myc level during antihormonal treatment. We further show that MECP2-expressing cells possess a functional p53 pathway and are still responsive to chemotherapeutic drugs.

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Acknowledgements

We thank members of Yvan de Launoit's laboratory for helpful discussions. We also thank S Kudo for the pcdMP4 vector and the RA7 MECP2 antibody. This work was carried out with the support of the FNRS (Belgium), the ‘Action de Recherche Concertée de la Communauté Française de Belgique’, ‘Fortis Bank assurances’ (Belgium), the ‘Fédération Belge Contre le Cancer’, the CNRS (France), the ARC (France), the FRM Nord Pas de Calais (France), the ‘Conseil Régional Nord/pas-de-Calais’ (France), and the European Regional Development Fund. JG is supported by Human Frontiers Science Program and Cancer Research UK. DB is supported by a Marie Curie Intra-European Fellowship within the sixth European Community Framework Program. FF is a ‘Chercheur Qualifié du FNRS’.

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Authors and Affiliations

  1. Molecular Virology Laboratory, Free University of Brussels, Brussels, Belgium

    D Bernard, F Fuks & Y de Launoit

  2. MRC Clinical Sciences Centre, Imperial College, Hammersmith, London, UK

    J Gil

  3. Régulation Transcriptionnelle au cours de la Tumorigenèse Mammaire, UMR 8117 – CNRS Université des Sciences et Technologie de Lille 1, Institut Pasteur de Lille/Institut de Biologie de Lille, Lille Cedex, France

    P Dumont, D Monté, B Quatannens & Y de Launoit

  4. Prostate Stem Cell Laboratory, Institute of Cancer Research, Sutton, UK

    S Rizzo & D Hudson

  5. Cancer Genetics, University of Tampere and Tampere University Hospital, University of Tampere, Tampere, Finland

    T Visakorpi

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Correspondence to D Bernard.

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Supplementary Information accompanies the paper on Oncogene website (http://www.nature.com/onc).

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Bernard, D., Gil, J., Dumont, P. et al. The methyl-CpG-binding protein MECP2 is required for prostate cancer cell growth. Oncogene 25, 1358–1366 (2006). https://doi.org/10.1038/sj.onc.1209179

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