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Rapid signalling by androgen receptor in prostate cancer cells

Oncogene volume 18, pages 6322–6329 (1999)Cite this article

Abstract

Androgens are important growth regulators in prostate cancer. Their known mode of action in target cells requires binding to a cytoplasmic androgen receptor followed by a nuclear translocation event and modulation of the expression of specific genes. Here, we report another mode of action of this receptor. Treatment of androgen responsive prostate cancer cells with dihydrotestosterone leads to a rapid and reversible activation of mitogen-activated protein kinases MAPKs (also called extracellular signal-regulated kinases or Erks). Transient transfection assays demonstrated that the androgen receptor-mediated activation of MAP kinase results in enhanced activity of the transcription factor Elk-1. This action of the androgen receptor differs from its known transcriptional activity since it is rapid and insensitive to androgen antagonists such as hydroxyflutamide or casodex. Biochemical studies as well as analyses with dominant negative mutants showed the involvement of kinases such as MAPK/Erk kinase, phosphatidyl-inositol 3-kinase and protein kinase C in the androgen receptor-mediated activation of MAP kinase. These results demonstrate a novel regulatory action of the androgen receptor and prove that in addition to its known transcriptional effects, it also uses non-conventional means to modulate several cellular signalling processes.

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Acknowledgements

We thank AO Brinkmann for anti-AR antibodies, P Shaw for supplying us with the constructs for the Gal 4 DBD-Elk-1 transfection assays and P Brennan for the dominant negative p85 PI3 kinase construct. We also thank E Metzinger for her help with the PI3 kinase assay. We acknowledge with thanks the excellent technical assistance of J Stober and A Hesselschwerdt. This work was supported by grants from the German Science Foundation and the Deutsche Krebshilfe.

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Authors and Affiliations

  1. Forschungszentrum Karlsruhe, Institut für Toxikologie und Genetik, 3640, D-76021, Postfach, Karlsruhe, Germany

    Heike Peterziel, Sigrun Mink, Annette Schonert, Matthias Becker & Andrew CB Cato

  2. Department of Urology, University of Innsbruck, 35, A-6020, Anichstrasse, Innsbruck, Austria

    Helmut Klocker

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  1. Heike Peterziel
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Peterziel, H., Mink, S., Schonert, A. et al. Rapid signalling by androgen receptor in prostate cancer cells. Oncogene 18, 6322–6329 (1999). https://doi.org/10.1038/sj.onc.1203032

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