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Influence of nucleophosmin/B23 on DNA binding and transcriptional activity of the androgen receptor in prostate cancer cell

Oncogene volume 27, pages 2858–2867 (2008)Cite this article

Abstract

The promotion and progression of prostate cancer (PCa) are associated with androgen receptor (AR) signalling. AR functions are modulated by a variety of co-factors amongst which we identified the nucleophosmin (NPM/B23), a member of the histone chaperone family. Here, we show that NPM is overexpressed in PCa compared to normal adjacent tissues. AR and NPM interact in vitro and in vivo, and NPM is critical for androgen-dependent transcriptional activation in LNCaP cells as an anti-NPM siRNA downregulates transcription of a transfected androgen response element (ARE)-containing reporter promoter as well as expression of the endogenous androgen responsive prostate-specific antigen (PSA) gene. By investigating the effect of NPM on AR, we have also observed that NPM enhances AR binding to an ARE in vitro in electrophoretic gel mobility-shift assay experiments. Chromatin immunoprecipitation studies further demonstrated that both AR and NPM associate with AREs of the PSA gene in vivo. Altogether, our data suggest that the molecular histone chaperone NPM could regulate AR functions by promoting assembly of AR-containing regulatory complexes and that high levels of NPM might alter AR functions in PCa.

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Acknowledgements

We are very grateful to J-P Saru, A de Haze for their technical assistance, A Bruhat for his pertinent advices for DNA ChIP. This work was supported by grants awarded by the Centre National de la Recherche Scientifique (CNRS), the Institut National du Cancer (grant PL06-125), Ligue Contre le Cancer Puy de Dôme and the Université Blaise Pascal (UBP). L Léotoing is recipient of a doctoral fellowship from the Association pour la Recherche sur le Cancer (ARC).

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Authors and Affiliations

  1. UMR 6547 CNRS—Université Blaise Pascal Clermont-Ferrand II, Aubière cedex, France

    L Léotoing, M Manin, G Veyssière, L Morel & C Beaudoin

  2. U 407 INSERM—Faculté de Médecine Lyon Sud, Oullins cedex, France

    L Meunier, C Mauduit, M Decaussin & M Benahmed

  3. Molecular Endocrinology Laboratory, Katholieke Universiteit Leuven, Leuven, Belgium

    G Verrijdt & F Claessens

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  1. L Léotoing
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  2. L Meunier
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  3. M Manin
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  4. C Mauduit
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  5. M Decaussin
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  6. G Verrijdt
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  9. G Veyssière
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  10. L Morel
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Correspondence to L Morel.

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

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Léotoing, L., Meunier, L., Manin, M. et al. Influence of nucleophosmin/B23 on DNA binding and transcriptional activity of the androgen receptor in prostate cancer cell. Oncogene 27, 2858–2867 (2008). https://doi.org/10.1038/sj.onc.1210942

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