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Androgen suppresses protein kinase D1 expression through fibroblast growth factor receptor substrate 2 in prostate

Liyong Zhang1, Zhenlong Zhao1,2, Shuping Xu1

  • 1Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Oncotarget
|January 13, 2017
PubMed

Insights

Androgen signaling represses Protein Kinase D1 (PKD1) in prostate cancer cells. This novel androgen-repressed gene, PKD1, may contribute to therapeutic resistance when upregulated by anti-androgens.

Area of Science:

  • Oncology
  • Molecular Biology
  • Endocrinology

Background:

  • Androgen signaling is crucial in prostate cancer progression.
  • Protein Kinase D (PKD) family, especially PKD1, is implicated in prostate cancer.
  • Understanding androgen-PKD1 interactions is vital for treatment strategies.

Purpose of the Study:

  • To investigate the cross-regulation between androgen signaling and PKD1 in prostate cancer cells.
  • To identify PKD1 as a novel androgen-regulated gene.
  • To elucidate the molecular pathway mediating androgen's effect on PKD1.

Main Methods:

  • Studied androgen-sensitive prostate cancer cells.
  • Utilized steroid depletion and AR agonist (R1881) treatments.
  • Performed kinetic analysis, AR inhibition/knockdown experiments.
  • Investigated downstream mediators including FRS2 and the MEK/ERK pathway.

Main Results:

  • Androgen represses PKD1 transcription and protein levels in prostate cancer cells.
  • PKD1 is identified as a novel androgen-repressed gene.
  • Androgen Receptor (AR) is essential for androgen-induced PKD1 repression.
  • The AR/FRS2/MEK/ERK pathway mediates androgen-induced PKD1 repression.

Conclusions:

  • PKD1 is a novel androgen-suppressed gene in prostate cancer.
  • Androgen downregulates PKD1 via the AR/FRS2/MEK/ERK pathway.
  • Upregulation of PKD1 by anti-androgens may drive therapeutic resistance in prostate cancer.
Keywords:
androgenandrogen receptorandrogen-repressed genesprostate cancerprotein kinase D1

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