Document Detail

DNA demethylase is expressed in ovarian cancers and the expression correlates with demethylation of CpG sites in the promoter region of c-erbB-2 and survivin genes.
MedLine Citation:
PMID:  11431104     Owner:  NLM     Status:  MEDLINE    
The objectives of this study were to examine DNA demethylase (dMTase) expression in ovarian cancers and evaluate methylation of CpG sites in the promoter of the c-erbB-2 gene and survivin gene exon 1. Forty-three epithelial ovarian cancers and 43 non-cancerous ovarian tissues were studied for dMTase expression by RT-PCR. Genomic DNA was extracted and digested with HindIII and then HpaII. CpG site-sensitive primers were constructed to amplify the promoter of the c-erbB-2 gene and survivin gene exon 1. Immunohistochemical evaluation of ErbB-2 protein and RT-PCR for survivin were also performed. dMTase was positive in 88.4% of ovarian cancers but only in 9.3% of non-cancerous ovaries (P<0.001, Fisher's exact test). The expression was similarly observed in both early stage (stage I+II: 17/19) and advanced stage (stage III+IV: 21/24) groups of ovarian malignancy. It was found that 78.9% of dMTase-positive cancers had both c-erbB-2 promoter and survivin gene exon 1 unmethylated, whereas 40% of dMTase-negative cancers had both sites methylated. In non-cancerous ovaries, these sites were mostly methylated (90.6%) and the difference from cancer cases was highly significant (P<0.001). Immunohistochemical evaluation of ErbB-2 showed significant correlation of unmethylated c-erbB-2 promoter and ErbB-2 expression. The RT-PCR for survivin expression showed that 86% of cancers were positive and six cases were negative. Exon 1 was methylated in 83% of the survivin-negative cases. This is the first report of dMTase expression in ovarian cancers. The correlation of dMTase expression with unmethylation of c-erbB-2 promoter and survivin gene exon 1 suggests that these sites may be targets for demethylation by the enzyme. The up-regulation of oncogenes may be the consequence of epigenetic control of gene expression by the dMTase.
M Hattori; H Sakamoto; K Satoh; T Yamamoto
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cancer letters     Volume:  169     ISSN:  0304-3835     ISO Abbreviation:  Cancer Lett.     Publication Date:  2001 Aug 
Date Detail:
Created Date:  2001-06-29     Completed Date:  2001-08-16     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  7600053     Medline TA:  Cancer Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  155-64     Citation Subset:  IM    
Department of Obstetrics and Gynecology, Nihon University School of Medicine, 30-1, Oyaguchi, Kamimachi, Itabashi, 173-0861, Tokyo, Japan.
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MeSH Terms
CpG Islands*
DNA / metabolism
DNA Methylation*
DNA, Complementary / metabolism
Microtubule-Associated Proteins*
Middle Aged
Neoplasm Proteins
Ovarian Neoplasms / genetics,  metabolism*
Ovary / pathology
Oxidoreductases, O-Demethylating / biosynthesis*
Polymerase Chain Reaction
Promoter Regions, Genetic*
Proteins / genetics*
Receptor, erbB-2 / genetics*
Reverse Transcriptase Polymerase Chain Reaction
Reg. No./Substance:
0/BIRC5 protein, human; 0/DNA, Complementary; 0/Microtubule-Associated Proteins; 0/Neoplasm Proteins; 0/Proteins; 9007-49-2/DNA; EC 1.-/Oxidoreductases, O-Demethylating; EC 1.-/methyl-CpG DNA demethylase; EC, erbB-2

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