Linked Life Data

16676400

Source:http://linkedlifedata.com/resource/pubmed/id/16676400

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2006-5-4
pubmed:abstractText
Nicotinamide N-methyltransferase (NNMT) catalyzes N-methylation of nicotinamide and other structural analogues. NNMT gene expression is enhanced in many papillary thyroid cancer cells and activated by hepatocyte nuclear factor (HNF)-1beta. In this work, we studied the effects of depsipeptide, a histone deacetylase inhibitor, on NNMT gene expression in BHP 18-21 papillary thyroid cancer cells. Depsipeptide reduced NNMT mRNA level in a dose-dependent and time-dependent manner as determined by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR). In contrast, expression of the sodium iodide symporter (NIS), a gene with differentiated function, waas enhanced in the treated cells. NNMT protein level determined by Western blot analysis and NNMT catalytic activity was also reduced significantly in the depsipeptide-treated cells. To study the mechanism of NNMT gene repression by depsipeptide, effects of depsipeptide on NNMT promoter activity were determined by luciferase reporter gene assay. NNMT promoter activity was significantly reduced in the HNF-1beta-positive BHP 18-21 cells but not in the HNF-1beta-negative BHP 14-9 papillary cancer cells. A mutant reporter construct with mutations in a HNF-1 site in the NNMT basal promoter region did not respond to depsipeptide in both HNF-1beta protein levels, and abolished activity of DNA binding to the HNF-1 site in the NNMT promoter region. Protein synthesis inhibitor cycloheximide and proteasome inhibitor MG-132 enhanced HNF-1beta stability in the depsipeptide-treated cells. In summary, depsipeptide represses NNMT and HNF-1beta gene expression in some papillary thyroid cancer cells. the repression of NNMT by depsipeptide is at the transcription level through downregulation of transcription activator HNF-1beta.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1050-7256
pubmed:author
pubmed:issnType
Print
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
151-60
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:16676400-Blotting, Western, pubmed-meshheading:16676400-Carcinoma, Papillary, pubmed-meshheading:16676400-Catalysis, pubmed-meshheading:16676400-Cell Line, Tumor, pubmed-meshheading:16676400-Cell Nucleus, pubmed-meshheading:16676400-Depsipeptides, pubmed-meshheading:16676400-Enzyme Inhibitors, pubmed-meshheading:16676400-Gene Expression Regulation, Neoplastic, pubmed-meshheading:16676400-Genes, Reporter, pubmed-meshheading:16676400-Hepatocyte Nuclear Factor 1-beta, pubmed-meshheading:16676400-Histone Deacetylase Inhibitors, pubmed-meshheading:16676400-Humans, pubmed-meshheading:16676400-Models, Statistical, pubmed-meshheading:16676400-Mutation, pubmed-meshheading:16676400-Nicotinamide N-Methyltransferase, pubmed-meshheading:16676400-Plasmids, pubmed-meshheading:16676400-Promoter Regions, Genetic, pubmed-meshheading:16676400-RNA, Messenger, pubmed-meshheading:16676400-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:16676400-Thyroid Neoplasms, pubmed-meshheading:16676400-Time Factors, pubmed-meshheading:16676400-Transcriptional Activation, pubmed-meshheading:16676400-Transfection
pubmed:year
2006
pubmed:articleTitle
Histone deacetylase inhibitor depsipeptide represses nicotinamide N-methyltransferase and hepatocyte nuclear factor-1beta gene expression in human papillary thyroid cancer cells.
pubmed:affiliation
Endocrinology and Diabetes Division, VA Greater Los Angeles Healthcare System, David Geffen School of Medicine at UCLA, CA, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S.