Epigenetic changes in prostate cancer: implication for diagnosis and treatment

J Natl Cancer Inst. 2005 Jan 19;97(2):103-15. doi: 10.1093/jnci/dji010.

Abstract

Prostate cancer is the most common noncutaneous malignancy and the second leading cause of cancer death among men in the United States. DNA methylation and histone modifications are important epigenetic mechanisms of gene regulation and play essential roles both independently and cooperatively in tumor initiation and progression. Aberrant epigenetic events such as DNA hypo- and hypermethylation and altered histone acetylation have both been observed in prostate cancer, in which they affect a large number of genes. Although the list of aberrantly epigenetically regulated genes continues to grow, only a few genes have, so far, given promising results as potential tumor biomarkers for early diagnosis and risk assessment of prostate cancer. Thus, large-scale screening of aberrant epigenetic events such as DNA hypermethylation is needed to identify prostate cancer-specific epigenetic fingerprints. The reversibility of epigenetic aberrations has made them attractive targets for cancer treatment with modulators that demethylate DNA and inhibit histone deacetylases, leading to reactivation of silenced genes. More studies into the mechanism and consequence of demethylation are required before the cancer epigenome can be safely manipulated with therapeutics as a treatment modality. In this review, we examine the current literature on epigenetic changes in prostate cancer and discuss the clinical potential of cancer epigenetics for the diagnosis and treatment of this disease.

Publication types

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

MeSH terms

  • Acyltransferases / genetics
  • Biomarkers, Tumor / genetics
  • DNA Damage / drug effects
  • DNA Methylation* / drug effects
  • DNA Repair / drug effects
  • Enzyme Inhibitors / pharmacology
  • Epigenesis, Genetic*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Silencing / drug effects
  • Genes, Tumor Suppressor
  • Genes, cdc / drug effects
  • Histone Deacetylases / drug effects
  • Histone Deacetylases / metabolism
  • Histones / metabolism*
  • Humans
  • Male
  • Prostatic Neoplasms / diagnosis*
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / genetics
  • Tumor Suppressor Proteins / genetics
  • Up-Regulation / drug effects

Substances

  • Biomarkers, Tumor
  • Enzyme Inhibitors
  • Histones
  • RASSF1 protein, human
  • Tumor Suppressor Proteins
  • Acyltransferases
  • fatty acyl ethyl ester synthase
  • Histone Deacetylases