Androgen receptor and heterogeneous nuclear ribonucleoprotein K colocalize in the nucleoplasm and are modulated by bicalutamide and 4-hydroxy-tamoxifen in prostatic cancer cell lines

Authors

  • Paola Barboro,

    1. Istituto Nazionale per la Ricerca sul Cancro, Università di Genova, Largo Rosanna Benzi, Genova, Italy
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  • Erica Repaci,

    1. Istituto Nazionale per la Ricerca sul Cancro, Università di Genova, Largo Rosanna Benzi, Genova, Italy
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  • Nicoletta Ferrari,

    1. Istituto Nazionale per la Ricerca sul Cancro, Università di Genova, Largo Rosanna Benzi, Genova, Italy
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  • Alessandra Rubagotti,

    1. Istituto Nazionale per la Ricerca sul Cancro, Università di Genova, Largo Rosanna Benzi, Genova, Italy
    2. Dipartimento di Oncologia, Biologia e Genetica, Università di Genova, Largo Rosanna Benzi, Genova, Italy
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  • Francesco Boccardo,

    1. Istituto Nazionale per la Ricerca sul Cancro, Università di Genova, Largo Rosanna Benzi, Genova, Italy
    2. Dipartimento di Oncologia, Biologia e Genetica, Università di Genova, Largo Rosanna Benzi, Genova, Italy
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  • Cecilia Balbi

    Corresponding author
    1. Istituto Nazionale per la Ricerca sul Cancro, Università di Genova, Largo Rosanna Benzi, Genova, Italy
    • Istituto Nazionale per la Ricerca sul Cancro, Largo Rosanna Benzi, 10-16132 Genova, Italy.
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Abstract

BACKGROUND

Bicalutamide (BIC) is widely used in prostate cancer therapy. The dose and schedule employed are well tolerated, but about 50% of patients develop gynecomastia. Several studies have shown a significant reduction of the troublesome effects when Tamoxifen is concomitantly administered with BIC. However, the results reported in the literature seem to be preliminary and possible interferences could be present. In order to clarify the molecular mechanisms of the combination of the two drugs, we have investigated whether the expression of the proteins belonging to nuclear matrix (NM), one modulator of hormone action, is altered by BIC and/or 4-hydroxy-tamoxifen (4OHT) in LNCaP cells. We focused above all on heterogeneous nuclear ribonucleoprotein K (hnRNP K) a NM protein with a key role in prostate carcinoma.

METHODS

NM proteins were analyzed by two-dimensional gel electrophoresis. Modulation and compartmentalization of the androgen receptor and the hnRNP K were studied by Western blotting, confocal microscopy, and immunoprecipitation.

RESULTS

Proteomic analysis revealed that there is a similarity in the changes of the NM proteins elicited by drugs alone but that their combination does not result in a simple additive effect. Moreover, we found that in the nucleoplasm the androgen receptor and the hnRNP K colocalize in a complex that is highly proximal to DNA and that both proteins were synchronously modulated by BIC and/or 4OHT treatment.

CONCLUSION

This study confirm the pivotal role of hnRNP K in prostate carcinoma and suggest that this role might be played by the interaction with the androgen receptor. Prostate 71:1466–1479, 2011. © 2011 Wiley-Liss, Inc.

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