Epigenetic regulation of Myc on retinoic acid receptor beta and PDLIM4 in RWPE1 cells.
BACKGROUND
Hypermethylation of CpG islands is a common epigenetic alteration associated with cancer. Tumor suppressor genes retinoic acid receptor beta (RARbeta) and PDLIM4 are hypermethylated and silenced in prostate cancer (PCa) tissues and PCa cell lines compared to normal prostate cells.


METHODS
In this study, a benign prostate epithelial cell line RWPE1 was used as a model to study the epigenetic regulation of Myc on the RARbeta and PDLIM4 promoters. Forced Myc overexpression inhibited the RARbeta and PDLIM4 expression.


RESULTS
Pyrosequencing study showed that Myc overexpression increased methylation in several CpG sites of both promoters. A DNA methylation inhibitor 5-aza-2'-deoxycytidine reversed the epigenetic alteration effect of Myc on both RARbeta and PDLIM4.


CONCLUSIONS
The epigenetic regulation of Myc may be related to its up-regulation of the DNA methyltransferase DNMT3a and DNMT3b.
He
Meilan
M
Department of Urology, Mayo Clinic, Rochester, Minnesota.
Vanaja
Donkena Krishna
DK
Karnes
R Jeffrey
RJ
Young
Charles Y F
CY
D015153:Blotting, Western; D048708:Cell Growth Processes / Q000235:genetics; D002460:Cell Line; D004247:DNA / Q000235:genetics; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism; D019175:DNA Methylation; D000090205:DNA Methyltransferase 3A; D004268:DNA-Binding Proteins / Q000235:genetics*; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D016259:Genes, myc; D006801:Humans; D060588:LIM Domain Proteins; D008297:Male; D016133:Polymerase Chain Reaction; D011467:Prostate / Q000201:enzymology / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014162:Transfection; D000097584:DNA Methyltransferase 3B
D004247:DNA; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; D018168:Receptors, Retinoic Acid; D000097584:DNA Methyltransferase 3B; C000717967:DNMT3A protein, human; C486247:PDLIM4 protein, human; C082925:retinoic acid receptor beta