1. ¹UMR 6547 CNRS—Université Blaise Pascal Clermont-Ferrand II, Aubière cedex, France
2. ²U 407 INSERM—Faculté de Médecine Lyon Sud, Oullins cedex, France
3. ³Molecular Endocrinology Laboratory, Katholieke Universiteit Leuven, Leuven, Belgium

Correspondence: Professor L Morel, UMR 6547 CNRS—Université Blaise Pascal Clermont-Ferrand II, 24 Avenue des Landais, Aubière Cedex 63177, France. E-mail: laurent.morel@univ-bpclermont.fr

Received 29 August 2007; Revised 12 October 2007; Accepted 17 October 2007; Published online 26 November 2007.

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.