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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2007-12-21
pubmed:abstractText
Brother of the Regulator of Imprinted Sites (BORIS/CTCFL) is an autosomal cancer germline (CG) or cancer-testis antigen gene and paralog of CTCF that has been proposed to function as an oncogene in human cancer via dysregulation of the cancer epigenome. Here we show that genetic disruption of DNA methylation in human cancer cells induces BORIS expression, coincident with DNA hypomethylation and an altered histone H3 modification pattern at the BORIS promoter. Rapid amplification of cDNA ends (RACE) mapping revealed that the transcriptional start site of BORIS in human testis, DNMT deficient human cancer cells, and human epithelial ovarian cancer (EOC) tissues, is similar and lies within the 5' CpG island. The BORIS promoter is repressed by CpG methylation in a dose-dependent fashion, indicating a direct role for DNA methylation in BORIS transcriptional regulation. In human ovarian cancer cell lines, 5-aza-2'-deoxycytidine treatment activates BORIS expression and reduces BORIS promoter DNA methylation. We quantitatively measured BORIS mRNA expression and promoter DNA methylation in normal ovary (NO; n = 10) and epithelial ovarian cancer (EOC; n = 77) and found that, compared to NO, EOC tumors show increased BORIS expression and decreased BORIS methylation. Importantly, BORIS promoter DNA methylation shows a significant inverse correlation with BORIS mRNA expression in EOC (Kendall's Tau = -0.235, P = 0.007, n = 63). These data establish promoter DNA hypomethylation as a mechanism leading to BORIS expression in human ovarian cancer.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1424-9634
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
21
pubmed:dateRevised
2011-9-26
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
DNA methylation-dependent regulation of BORIS/CTCFL expression in ovarian cancer.
pubmed:affiliation
Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural