Alterations of androgen receptor in prostate cancer

J Steroid Biochem Mol Biol. 2004 Nov;92(4):255-64. doi: 10.1016/j.jsbmb.2004.10.012. Epub 2004 Dec 19.

Abstract

The significance of androgens in the development of prostate cancer has been known for more than half century. During the last decade, a lot of effort has been put to study the significance of the specific nuclear receptor of the hormone, androgen receptor (AR). It has been suggested that polymorphisms, especially the length of CAG repeat in exon 1 of the gene, are associated with the risk of prostate cancer. However, not all studies have confirmed the association. Most surprisingly, it has now become clear that prostate carcinomas emerging during the androgen withdrawal therapy (i.e. hormone-refractory tumors) are capable of reactivating the AR-mediated signalling despite of the low levels of androgens. In addition, it has been shown that AR gene itself is genetically targeted. One-third of the hormone-refractory prostate carcinomas contains amplification of the gene. In addition, 10-30% of prostate carcinomas treated by antiandrogens acquire point mutation in the AR gene. The genetic alterations in AR indicate that receptor should be considered as putative treatment target. Evidently, the currently available antiandrogens are not capable to abolish the AR-mediated signalling efficiently enough.

Publication types

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

MeSH terms

  • Androgen Antagonists / therapeutic use
  • Drug Resistance, Neoplasm / genetics
  • Gene Amplification
  • Gene Expression Regulation, Neoplastic
  • Germ Cells / metabolism
  • Humans
  • Male
  • Models, Biological
  • Mutation
  • Neoplasms, Hormone-Dependent / drug therapy
  • Neoplasms, Hormone-Dependent / genetics
  • Polymorphism, Genetic
  • Prostatic Neoplasms / etiology*
  • Prostatic Neoplasms / genetics
  • Receptor, ErbB-2 / physiology
  • Receptors, Androgen / genetics*
  • Receptors, Androgen / physiology
  • Signal Transduction / physiology

Substances

  • Androgen Antagonists
  • Receptors, Androgen
  • Receptor, ErbB-2