Altered methylation of multiple genes in carcinogenesis of the prostate

Int J Cancer. 2003 Sep 1;106(3):382-7. doi: 10.1002/ijc.11227.

Abstract

The methylation status of 7 genes was examined in four cell lines, 36 samples of benign prostatic hyperplasia (BPH), 20 samples of prostatic intraepithelial neoplasia (PIN) and 109 samples of prostate cancer (PCa), using methylation-specific PCR (MSP): the pi-class glutathione S-transferase (GSTP1), retinoic acid receptor beta 2(RARbeta2), androgen receptor (AR), death-associated protein kinase (DAPK), tissue inhibitor of metalloproteinase-3 (TIMP-3), O(6)-methylguanine DNA methyltransferase (MGMT), and hypermethylated in cancer-1 (HIC-1). The frequencies of methylation in PCa were 88% for GSTP1, 78% for RARbeta2, 36% for DAPK, 15% for AR, 6% for TIMP-3, and 2% for MGMT, whereas the values were 11% for AR and DAPK, 6% for TIMP-3, 3% for GSTP1, and 0 for RARbeta2 and MGMT in BPH. Aberrant methylation of the GSTP1 and RARbeta2 genes was detected in 30% and 20% of PIN, respectively. Most samples of BPH and PCa were positive for HIC-1 methylation. Regarding accumulation of methylated cancer-related genes, there were significant correlations between PCa and BPH as well as PIN and BPH. In the present study, a high frequency of aberrant promoter methylation of the GSTP1 and RARbeta2 genes was noted in PCa. Our findings suggest that methylation of cancer-related genes may be involved in carcinogenesis of the prostate.

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Apoptosis Regulatory Proteins
  • Biomarkers, Tumor / genetics*
  • Calcium-Calmodulin-Dependent Protein Kinases / genetics
  • DNA Methylation*
  • DNA Primers / chemistry
  • Death-Associated Protein Kinases
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Glutathione S-Transferase pi
  • Glutathione Transferase / genetics
  • Humans
  • Isoenzymes / genetics
  • Male
  • Middle Aged
  • Neoplasm Proteins / genetics*
  • O(6)-Methylguanine-DNA Methyltransferase / genetics
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic / genetics*
  • Prostate-Specific Antigen / genetics
  • Prostatic Hyperplasia / enzymology
  • Prostatic Hyperplasia / genetics
  • Prostatic Hyperplasia / pathology
  • Prostatic Intraepithelial Neoplasia / enzymology
  • Prostatic Intraepithelial Neoplasia / genetics
  • Prostatic Intraepithelial Neoplasia / pathology
  • Prostatic Neoplasms / enzymology
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology
  • Receptors, Androgen / genetics
  • Receptors, Retinoic Acid / genetics
  • Tissue Inhibitor of Metalloproteinase-3 / genetics

Substances

  • Apoptosis Regulatory Proteins
  • Biomarkers, Tumor
  • DNA Primers
  • Isoenzymes
  • Neoplasm Proteins
  • Receptors, Androgen
  • Receptors, Retinoic Acid
  • Tissue Inhibitor of Metalloproteinase-3
  • retinoic acid receptor beta
  • O(6)-Methylguanine-DNA Methyltransferase
  • GSTP1 protein, human
  • Glutathione S-Transferase pi
  • Glutathione Transferase
  • Death-Associated Protein Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Prostate-Specific Antigen