Linked Life Data

20228127

Source:http://linkedlifedata.com/resource/pubmed/id/20228127

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2010-4-22
pubmed:abstractText
Radioiodine remains the only tumoricidal therapy for disseminated thyroid carcinomas; however, dedifferentiated tumors lose the expression of human sodium-iodide symporter (hNIS) gene, and cannot respond to this treatment. Previous studies suggested that a trans-active protein factor (NIS-repressor) represses endogenous hNIS transcription, likely contributing to the loss of radioiodine uptake, and defined the NIS-repressor binding site (NRBS) in the proximal hNIS promoter. Using electrophoretic mobility shift assay (EMSA), we found evidence of NIS-repressor in the nuclear extract from KAK-1 cells, and confirmed this result using nuclear extracts prepared from multiple verified thyroid cell lines. Luciferase reporter assays of hNIS promoter constructs and EMSA were used to define two core sequences, NRBS-P and NRBS-D, in the hNIS promoter as the binding sites for NIS-repressor. Electrophoretic analysis of KAK-1 nuclear extract proteins cross-linked with NRBS-P suggests that NIS-repressor is a protein complex. Analysis of KAK-1 nuclear extract proteins bound to NRBS-P, via liquid chromatography coupled with tandem mass spectroscopy, demonstrated poly(ADP-ribose) polymerase-1 (PARP-1) as a NIS-repressor component. Pharmacological inhibition of PARP-1 enzymatic activity using PJ34 stimulated both the luciferase reporter activity driven by hNIS promoter and the endogenous hNIS mRNA level. Supershift studies suggest that thyroid transcription factor 2 (TTF-2) is also associated with the NIS-repressor complex. NIS-repressor, including its PARP-1 component, presents a potential therapeutic target to restore radioiodine uptake in dedifferentiated thyroid carcinomas.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1479-6821
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
17
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
383-98
pubmed:dateRevised
2011-4-20
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Human sodium-iodide symporter (hNIS) gene expression is inhibited by a trans-active transcriptional repressor, NIS-repressor, containing PARP-1 in thyroid cancer cells.
pubmed:affiliation
Veterans Affairs Medical Center, Lexington, Kentucky 40511, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural