Epigenetic regulation of Myc on retinoic acid receptor beta and PDLIM4 in RWPE1 cells.

Abstract

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.

CONCLUSION:

The epigenetic regulation of Myc may be related to its up-regulation of the DNA methyltransferase DNMT3a and DNMT3b.

• Authors: Meilan He, Donkena Krishna Vanaja, R Jeffrey Karnes, Charles Y F Young
• Journal: The Prostate (Prostate) Vol. 69 Issue 15 Pg. 1643-50 (Nov 01 2009) ISSN: 1097-0045 [Electronic] United States
• PMID: 19623543 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• DNA-Binding Proteins
• DNMT3A protein, human
• LIM Domain Proteins
• PDLIM4 protein, human
• Receptors, Retinoic Acid
• retinoic acid receptor beta
• DNA
• DNA (Cytosine-5-)-Methyltransferases
• DNA Methyltransferase 3A
• DNA methyltransferase 3B

Topics

• Blotting, Western
• Cell Growth Processes (genetics)
• Cell Line
• DNA (genetics)
• DNA (Cytosine-5-)-Methyltransferases (metabolism)
• DNA Methylation
• DNA Methyltransferase 3A
• DNA-Binding Proteins (genetics)
• Epigenesis, Genetic
• Gene Expression Profiling
• Genes, myc
• Humans
• LIM Domain Proteins
• Male
• Polymerase Chain Reaction
• Prostate (enzymology, physiology)
• Prostatic Neoplasms (genetics, pathology)
• Receptors, Retinoic Acid (genetics)
• Sequence Analysis, DNA
• Transfection