Linked Life Data

17548962

Source:http://linkedlifedata.com/resource/pubmed/id/17548962

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2007-6-5
pubmed:abstractText
From a developmental point of view, human testicular germ cell tumor (TGCT) can be traced back to the primordial germ cells in the embryo, which, upon transformation, become either seminoma or non-seminoma. Thus, TGCT provides a useful model system for the study of gene regulation involved in oncogenesis as well as development. In this study, we focused and analyzed the expression and epigenetic alteration of DNA-methyltransferase (DNMT) genes in TGCT tissues. The examined genes included DNMT1, DNMT3A and DNMT3B that function to maintain or generate a methylation status of genomic DNA. Using semi-quantitative reverse transcription-polymerase chain reaction, we found that the expression of DNMT3A, but not DNMT1 or DNMT3B, was up-regulated markedly in TGCT specimens compared to non-tumor testicular tissues. To explore mechanisms involved in the up-regulation of DNMT3A, we examined the methylation status of CpGs in the gene. The distal and proximal promoter regions of DNMT3A were non-methylated in both TGCT and non-tumor tissues. In contrast, non-tumor testicular tissues exhibited a mixture of methylated and non-methylated CpGs in intron 25 of DNMT3A, whereas most CpGs in intron 25 were demethylated in TGCT specimens. This difference in the degree of methylation was confirmed by Southern blot analysis, in which an EcoRI site in intron 25 could be digested only when the CpG was non-methylated. Thus, epigenetic alteration of intron 25 toward de-methylation is associated with increased expression of DNMT3A in TGCT. The intron 25 may represent a differentially-methylated region in DNMT3A that is modulated during development and/or tumorigenesis of germ cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0040-8727
pubmed:author
pubmed:issnType
Print
pubmed:volume
212
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
177-90
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Up-regulation of DNA-methyltransferase 3A expression is associated with hypomethylation of intron 25 in human testicular germ cell tumors.
pubmed:affiliation
Department of Molecular Immunology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't