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


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.


CONCLUSIONS
Although promoter methylation represses PSMA transcription in LNCaP cells, another method inhibits PSMA expression in DU145 and PC3 cells.
Noss
Kenneth R
KR
Research Service, Overton Brooks Veterans Affairs Medical Center, Shreveport, Louisiana 71101-4295, USA.
Singal
Rakesh
R
Grimes
Sidney R
SR
D000954:Antigens, Surface; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001483:Base Sequence; D002268:Carboxypeptidases / Q000096:biosynthesis / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D000077209:Decitabine; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017930:Genes, Reporter; D043425:Glutamate Carboxypeptidase II; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation / Q000187:drug effects; D014162:Transfection; D014407:Tumor Cells, Cultured
D000954:Antigens, Surface; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; C012589:trichostatin A; D000077209:Decitabine; D008156:Luciferases; D002268:Carboxypeptidases; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II; D001374:Azacitidine