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Heat shock protein 27 mediates repression of androgen receptor function by protein kinase D1 in prostate cancer cells

Oncogene volume 28, pages 4386–4396 (2009)Cite this article

Abstract

We have previously shown that protein kinase D1 (PKD1), charter member of PKD protein family, is downregulated in advanced prostate cancer (PC) and influences androgen receptor (AR) function in PC cells. Other independent studies showed that serine 82 residue in heat shock protein 27 (Hsp27) undergoes substrate phosphorylation by PKD1 and is associated with nuclear transport of AR resulting in increased AR transcriptional activity. In this study, we show that PKD1 interacts and phosphorylates Hsp27 at Ser82 in PC cells, which is mediated by p38-dependent mitogen-activated protein kinase pathway and is necessary for PKD1 repression of AR transcriptional activity and androgen-dependent proliferation of PC cells. The study provides first in vivo evidence that Hsp27 is a mediator of repression of AR function by PKD1 in PC cells, thereby linking the data in the published literature.

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Acknowledgements

We thank Dr FJ Johannes, Fraunhofer Institute for Interfacial Engineering, Stuttgart, Germany for providing the PKD1 expression vector. This study was supported by an institutional grant from the Department of Surgery, University of Massachusetts Medical School.

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  1. S Hassan and M H U Biswas: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Urology, Department of Surgery, University of Massachusetts Medical School, Worcester, MA, USA

    S Hassan, M H U Biswas, C Zhang, C Du & K C Balaji

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  1. S Hassan
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Correspondence to K C Balaji.

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Hassan, S., Biswas, M., Zhang, C. et al. Heat shock protein 27 mediates repression of androgen receptor function by protein kinase D1 in prostate cancer cells. Oncogene 28, 4386–4396 (2009). https://doi.org/10.1038/onc.2009.291

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