Mini-review: Foldosome regulation of androgen receptor action in prostate cancer

Mol Cell Endocrinol. 2013 Apr 30;369(1-2):52-62. doi: 10.1016/j.mce.2013.01.023. Epub 2013 Feb 8.

Abstract

Steroid hormone receptors play diverse roles in many aspects of human physiology including cell division, apoptosis and homeostasis, tissue differentiation, sexual development and response to stress. These ligand-activated transcription factors require the functional activity of numerous chaperone and chaperone-associated proteins, collectively termed the foldosome, at the crucial step of ligand recognition and binding. Since the initial isolation of foldosome components and pioneering research by Pratt, Toft and colleagues we understand much regarding cytosolic receptor function. The classical view, that the role of foldosome components is restricted to the cytosol, has been modified over recent years by research highlighting additional roles of chaperone proteins in nuclear translocation and target gene expression. Further, dysregulation of chaperone activity and expression has been implicated in various cancers, including breast and prostate cancer. Consequently, the foldosome provides an attractive therapeutic target in steroid hormone receptor-driven malignancies. This review summarises current knowledge of how the foldosome impacts upon androgen receptor signalling, which is the key therapeutic target on prostate cancer, and how foldosome components may be used as biomarkers or therapeutic targets in this disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Binding Sites
  • Cell Nucleus / metabolism
  • Gene Expression Regulation, Neoplastic
  • HSP90 Heat-Shock Proteins / antagonists & inhibitors
  • HSP90 Heat-Shock Proteins / metabolism
  • HSP90 Heat-Shock Proteins / physiology
  • Heat-Shock Proteins / metabolism
  • Heat-Shock Proteins / physiology
  • Humans
  • Intramolecular Oxidoreductases / antagonists & inhibitors
  • Intramolecular Oxidoreductases / metabolism
  • Intramolecular Oxidoreductases / physiology
  • Male
  • Models, Biological
  • Molecular Chaperones / physiology*
  • Prostaglandin-E Synthases
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / therapy
  • Receptors, Androgen / chemistry
  • Receptors, Androgen / metabolism*
  • Signal Transduction
  • Triterpenes / pharmacology

Substances

  • HSP90 Heat-Shock Proteins
  • Heat-Shock Proteins
  • Molecular Chaperones
  • Receptors, Androgen
  • Triterpenes
  • Intramolecular Oxidoreductases
  • Prostaglandin-E Synthases
  • tripterine