Linked Life Data

10404820

Source:http://linkedlifedata.com/resource/pubmed/id/10404820

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
1999-7-26
pubmed:abstractText
Disseminated dedifferentiated thyroid epithelial carcinoma, which cannot sufficiently concentrate therapeutic radioiodide, is a terminal disease without any effective systemic treatment or chemotherapy. This is a likely consequence of loss of human sodium-iodide symporter (hNIS) function. We hypothesized that hNIS transcriptional failure in thyroid carcinoma could be consequent to methylation of DNA in critical regulatory regions and could be reversed with chemical demethylation treatment. Analysis of hNIS messenger ribonucleic acid (mRNA) expression in 23 tumor samples revealed that although loss of this expression corresponded to loss of clinical radioiodide uptake, some thyroid carcinomas with hNIS mRNA expression did not concentrate iodide, suggesting additional posttranscriptional mechanisms for loss of hNIS function. In addition, analysis of DNA methylation in CpG-rich regions of the hNIS promoter extending to the first intron failed to define specific methylation patterns associated with transcriptional failure in human thyroid tumor samples. In seven human thyroid carcinoma cell lines lacking hNIS mRNA, treatment with 5-azacytidine or sodium butyrate was able to restore hNIS mRNA expression in four cell lines and iodide transport in two cell lines. Investigation of methylation patterns in these cell lines revealed that successful restoration of hNIS transcription was associated with demethylation of hNIS DNA in the untranslated region within the first exon. This was also associated with restoration of expression of thyroid transcription factor-1. These results suggest a role for DNA methylation in loss of hNIS expression in thyroid carcinomas as well as a potential application for chemical demethylation therapy in restoring responsiveness to therapeutic radioiodide.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0021-972X
pubmed:author
pubmed:issnType
Print
pubmed:volume
84
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2449-57
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:10404820-Adenoma, pubmed-meshheading:10404820-Antimetabolites, Antineoplastic, pubmed-meshheading:10404820-Azacitidine, pubmed-meshheading:10404820-Butyrates, pubmed-meshheading:10404820-Carcinoma, Papillary, pubmed-meshheading:10404820-Carrier Proteins, pubmed-meshheading:10404820-DNA, pubmed-meshheading:10404820-DNA Methylation, pubmed-meshheading:10404820-Gene Expression, pubmed-meshheading:10404820-Humans, pubmed-meshheading:10404820-Iodides, pubmed-meshheading:10404820-Membrane Proteins, pubmed-meshheading:10404820-Promoter Regions, Genetic, pubmed-meshheading:10404820-RNA, Messenger, pubmed-meshheading:10404820-Symporters, pubmed-meshheading:10404820-Thyroid Neoplasms, pubmed-meshheading:10404820-Transcription, Genetic, pubmed-meshheading:10404820-Tumor Cells, Cultured
pubmed:year
1999
pubmed:articleTitle
Restoration of iodide uptake in dedifferentiated thyroid carcinoma: relationship to human Na+/I-symporter gene methylation status.
pubmed:affiliation
Thyroid Cancer Research Laboratory, Medical Service, Veterans Affairs Medical Center, Lexington, Kentucky 40511, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't