| 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. | |
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MedLine Citation:
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PMID: 11431104 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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M Hattori; H Sakamoto; K Satoh; T Yamamoto |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Cancer letters Volume: 169 ISSN: 0304-3835 ISO Abbreviation: Cancer Lett. Publication Date: 2001 Aug |
Date Detail:
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Created Date: 2001-06-29 Completed Date: 2001-08-16 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 7600053 Medline TA: Cancer Lett Country: Ireland |
Other Details:
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Languages: eng Pagination: 155-64 Citation Subset: IM |
Affiliation:
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Department of Obstetrics and Gynecology, Nihon University School of Medicine, 30-1, Oyaguchi, Kamimachi, Itabashi, 173-0861, Tokyo, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adult Aged CpG Islands* DNA / metabolism DNA Methylation* DNA, Complementary / metabolism Exons Female Humans Immunohistochemistry 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 Temperature |
| Chemical | |
Reg. No./Substance:
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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 2.7.10.1/Receptor, erbB-2 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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