Linked Life Data

12508241

Source:http://linkedlifedata.com/resource/pubmed/id/12508241

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2002-12-31
pubmed:abstractText
The CD44 adhesion receptor is silenced in highly malignant neuroblastomas (NBs) with MYCN amplification. Because its functional expression is associated with decreased tumorigenic properties, CD44 behaves as a tumor suppressor gene in NB and other cancers. Given that the precise mechanisms responsible for CD44 silencing are not elucidated, we investigated whether CD44 expression could be regulated by DNA hypermethylation. The methylation status of CD44 gene promoter and exon 1 regions was analyzed in 12 NB cell lines and 21 clinical samples after bisulfite genomic modification, followed by PCR and single-strand conformation polymorphism analysis and genomic sequencing. The results showed that almost all CD44-negative cell lines displayed hypermethylation in both regions, whereas all CD44-expressing cell lines were unmethylated. These observations correlated with the ability to restore CD44 mRNA and protein expression by treatment of CD44-negative cells with the 5-aza-2'-deoxycytidine demethylating agent. In contrast, no CD44 gene hypermethylation could be detected in 21 NB clinical samples of different stages, irrespective of CD44 expression. Although our results suggest that aberrant methylation of promoter and exon 1 regions is involved in CD44 silencing in NB cell lines, they also indicate that methylation of unidentified regulatory sequences or methylation-independent mechanisms also control the expression of CD44 in primary NB tumors and cell lines. We therefore conclude that CD44 silencing is controlled by complex and tumor cell-specific processes, including gene hypermethylation. Further investigation of other mechanisms and genes involved in CD44 regulation will be needed before demethylation-mediated reactivation of the CD44 gene can be considered as therapeutic strategy for neuroblastoma and perhaps other related cancers.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1045-2257
pubmed:author
pubmed:copyrightInfo
Copyright 2003 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:volume
36
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
129-38
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:12508241-Antigens, CD44, pubmed-meshheading:12508241-Azacitidine, pubmed-meshheading:12508241-Bone Marrow Neoplasms, pubmed-meshheading:12508241-CpG Islands, pubmed-meshheading:12508241-DNA Methylation, pubmed-meshheading:12508241-DNA Modification Methylases, pubmed-meshheading:12508241-Exons, pubmed-meshheading:12508241-Gene Amplification, pubmed-meshheading:12508241-Gene Expression Regulation, pubmed-meshheading:12508241-Gene Silencing, pubmed-meshheading:12508241-Humans, pubmed-meshheading:12508241-Immunohistochemistry, pubmed-meshheading:12508241-Neoplasm Staging, pubmed-meshheading:12508241-Neuroblastoma, pubmed-meshheading:12508241-Nuclear Proteins, pubmed-meshheading:12508241-Oncogene Proteins, pubmed-meshheading:12508241-Promoter Regions, Genetic, pubmed-meshheading:12508241-Tumor Cells, Cultured
pubmed:year
2003
pubmed:articleTitle
Hypermethylation-mediated regulation of CD44 gene expression in human neuroblastoma.
pubmed:affiliation
Department of Pediatrics, University Hospital (CHUV), Lausanne, Switzerland.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't