Androgen receptor (AR) inhibitor ErbB3-binding protein-1 (Ebp1) is not targeted by the newly identified AR controlling signaling axis heat-shock protein HSP27 and microRNA miR-1 in prostate cancer cells

World J Urol. 2015 Mar;33(3):323-7. doi: 10.1007/s00345-014-1307-4. Epub 2014 May 6.

Abstract

Purpose: Androgen receptor (AR) networks are predominantly involved in prostate cancer (PCa) progression; consequently, factors of AR regulation represent promising targets for PCa therapy. The ErbB3-binding protein 1 (Ebp1) is linked to AR suppression and chemoresistance by so far unknown mechanisms. In this study, an assumed regulation of Ebp1 by the newly identified AR controlling signaling axis heat-shock protein 27 (HSP27)-microRNA-1 (miR-1) was examined.

Methods: Transfection experiments were carried out overexpressing and knockdown HSP27 and miR-1, respectively, in LNCaP and PC-3 cells. Afterward, HSP27- and miR-1-triggered Ebp1 protein expression was monitored by Western blotting.

Results: AR-positive LNCaP cells and AR-negative PC-3 cells possessed diverse basal expression levels of Ebp1. However, subsequent studies revealed no differences in cellular Ebp1 concentrations after modulation of HSP27 and miR-1. Furthermore, docetaxel incubation experiments exhibited no effects on Ebp1 protein synthesis.

Conclusion: In PCa, Ebp1 has been described as a regulator of AR functionality and as an effector of PCa therapy resistance. Our data suggest that Ebp1 functionality is independent from heat-shock-protein-regulated progression networks in PCa.

Publication types

  • Comparative Study

MeSH terms

  • Adaptor Proteins, Signal Transducing / physiology*
  • Adenocarcinoma / pathology
  • Adenocarcinoma / physiopathology*
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / physiology
  • Cells, Cultured
  • Disease Progression
  • Gene Expression Regulation, Neoplastic / physiology
  • HSP27 Heat-Shock Proteins / physiology*
  • Humans
  • Male
  • MicroRNAs / physiology*
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / physiopathology*
  • RNA-Binding Proteins / physiology*
  • Receptors, Androgen / drug effects
  • Receptors, Androgen / physiology*
  • Signal Transduction / physiology*
  • Transfection

Substances

  • Adaptor Proteins, Signal Transducing
  • Antineoplastic Agents
  • HSP27 Heat-Shock Proteins
  • MIRN1 microRNA, human
  • MicroRNAs
  • PA2G4 protein, human
  • RNA-Binding Proteins
  • Receptors, Androgen