Epigenetic regulation of a novel tumor suppressor gene (hDAB2IP) in prostate cancer cell lines.
hDAB2IP (human DAB2 (also known as DOC-2) interactive protein) is a novel GTPase-activating protein for modulating the Ras-mediated signal pathway. We demonstrate that the down-regulation of hDAB2IP mRNA in prostate cancer (PCa) cells is regulated by transcriptional levels. Analysis of the hDAB2IP promoter revealed that it is a typical TATA-less promoter containing many GC-rich sequences. In this study, we delineated the potential impact of the epigenetic control of the hDAB2IP promoter on its gene regulation in PCa. Acetylhistone H3 was associated with the hDAB2IP promoter, and CpG islands remained almost unmethylated in normal prostatic epithelia, but not in PCa cell lines. Our data further indicated that trichostatin A (histone deacetylase inhibitor) and 5'-aza-2'-deoxycytidine (DNA hypomethylation agent) acted cooperatively in modulating hDAB2IP gene expression in PCa, whereas histone acetylation played a more significant role in this event. Moreover, a core promoter sequence from the hDAB2IP gene responsible for these treatments was identified. We therefore conclude that epigenetic regulation plays a potential role in regulating hDAB2IP expression in PCa and that these results also provide a new therapeutic strategy for PCa patients.
Chen
Hong
H
Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9110, USA.
Toyooka
Shinichi
S
Gazdar
Adi F
AF
Hsieh
Jer-Tsong
JT
D001483:Base Sequence; D019175:DNA Methylation; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000235:genetics; D015226:Dinucleoside Phosphates / Q000737:chemistry; D004847:Epithelial Cells / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016385:TATA Box; D014407:Tumor Cells, Cultured; D020703:ras GTPase-Activating Proteins / Q000235:genetics*
D017931:DNA Primers; D004273:DNA, Neoplasm; D015226:Dinucleoside Phosphates; D020703:ras GTPase-Activating Proteins; C462952:DAB2IP protein, human; C015772:CpG dinucleotide