Methylation state of the prostate specific membrane antigen (PSMA) CpG island in prostate cancer cell lines

Anticancer Res. May-Jun 2002;22(3):1505-11.

Abstract

Background: PSMA expression varies among prostate cell lines. We examined the role of CpG methylation and histone deacetylation in PSMA transcriptional repression in prostate cell lines.

Materials and methods: The methylation status of a PSMA CpG island was investigated in LNCaP, DU145 and PC3 prostate cell lines. Cells were treated with a demethylating agent and a histone deacetylase inhibitor to determine if PSMA transcription could be activated in nonexpressing cells. A transfection assay with methylated and unmethylated PSMA promoter/enhancer-driven luciferase expression constructs was performed to examine the effect of methylation on transcription.

Results: The PSMA CpG island was only methylated in DU145 cells but transcription could not be activated by demethylation or histone deacetylase inhibition. Methylation repressed PSMA transcription in LNCaP cells.

Conclusion: Although promoter methylation represses PSMA transcription in LNCaP cells, another method inhibits PSMA expression in DU145 and PC3 cells.

Publication types

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

MeSH terms

  • Antigens, Surface*
  • Azacitidine / analogs & derivatives*
  • Azacitidine / pharmacology
  • Base Sequence
  • Carboxypeptidases / biosynthesis
  • Carboxypeptidases / genetics*
  • CpG Islands
  • DNA Methylation*
  • Decitabine
  • Enzyme Inhibitors / pharmacology
  • Genes, Reporter
  • Glutamate Carboxypeptidase II
  • Humans
  • Hydroxamic Acids / pharmacology
  • Luciferases / genetics
  • Luciferases / metabolism
  • Male
  • Molecular Sequence Data
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / metabolism
  • Transcription, Genetic
  • Transcriptional Activation / drug effects
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Antigens, Surface
  • Enzyme Inhibitors
  • Hydroxamic Acids
  • trichostatin A
  • Decitabine
  • Luciferases
  • Carboxypeptidases
  • FOLH1 protein, human
  • Glutamate Carboxypeptidase II
  • Azacitidine