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

S Hassan1, M H U Biswas, C Zhang

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

Oncogene
|September 22, 2009
PubMed

Insights

Protein kinase D1 (PKD1) represses androgen receptor (AR) activity in prostate cancer (PC) by phosphorylating heat shock protein 27 (Hsp27). This interaction, mediated by the p38 pathway, inhibits PC cell proliferation.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Signaling

Background:

  • Protein kinase D1 (PKD1) is downregulated in advanced prostate cancer (PC) and affects androgen receptor (AR) function.
  • PKD1 phosphorylates heat shock protein 27 (Hsp27) at serine 82, influencing AR nuclear transport and transcriptional activity.

Purpose of the Study:

  • To investigate the role of Hsp27 as a mediator in PKD1's repression of AR transcriptional activity and prostate cancer cell proliferation.
  • To elucidate the signaling pathway involved in PKD1-mediated Hsp27 phosphorylation.

Main Methods:

  • Co-immunoprecipitation assays to demonstrate interaction between PKD1 and Hsp27.
  • Western blotting to detect Hsp27 phosphorylation at Ser82.
  • Analysis of AR transcriptional activity and prostate cancer cell proliferation under various conditions.

Main Results:

  • PKD1 directly interacts with and phosphorylates Hsp27 at Ser82 in prostate cancer cells.
  • This phosphorylation is dependent on the p38-mitogen-activated protein kinase pathway.
  • PKD1-mediated Hsp27 phosphorylation is essential for the repression of AR transcriptional activity and androgen-dependent prostate cancer cell proliferation.

Conclusions:

  • Heat shock protein 27 (Hsp27) acts as a key mediator in the repression of androgen receptor (AR) function by protein kinase D1 (PKD1) in prostate cancer cells.
  • The p38-dependent phosphorylation of Hsp27 by PKD1 is a critical mechanism controlling AR activity and prostate cancer cell growth.
  • This study provides in vivo evidence linking PKD1, Hsp27, and AR signaling in prostate cancer progression.

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