Linked Life Data

11406558

Source:http://linkedlifedata.com/resource/pubmed/id/11406558

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2001-6-14
pubmed:abstractText
Methylation of the glutathione S-transferase P1 (GSTP1) gene has been described as a highly specific and sensitive biomarker for prostate cancer. However, at present, it is not known whether methylation represses GSTP1 gene expression in human prostate cancer. We found the GSTP1 gene promoter to be completely methylated in the LNCaP prostate cancer cell line, where this gene is transcriptionally inactive. In contrast, Du145 and PC3 prostate cancer cells express the GSTP1 gene and exhibit methylated and unmethylated GSTP1 alleles. In a transient transfection assay using LNCaP cells, methylation of the GSTP1 promoter-driven luciferase reporter vector (GSTP1-pGL3) resulted in a >20-fold inhibition of transcription, and this repression was not relieved by the presence of a histone deacetylase inhibitor, trichostatin A (TSA). Treatment of LNCaP cells with a DNA methyltransferase inhibitor, 5-Aza-2'-deoxycytidine, resulted in demethylation and activation of the GSTP1 gene. In contrast, TSA treatment failed to demethylate or activate the GSTP1 gene. Fully methylated but not unmethylated GSTP1 promoter fragment was shown to bind to a complex similar to methyl cytosine-binding protein complex 1 that contains methyl-CpG-binding domain 2 protein (MBD2) in electrophoretic mobility shift assays using LNCaP cell nuclear extracts. These data demonstrate that cytosine methylation can repress GSTP1 gene expression in LNCaP prostate cancer cells and that this effect is possibly mediated by a methyl cytosine-binding protein complex 1-like complex. Furthermore, these data also support the notion of the dominance of methylation over TSA-sensitive histone deacetylation in silencing genes with a high CpG density in the promoter region.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
61
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4820-6
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:11406558-Azacitidine, pubmed-meshheading:11406558-Base Sequence, pubmed-meshheading:11406558-Cytosine, pubmed-meshheading:11406558-DNA Methylation, pubmed-meshheading:11406558-Enzyme Inhibitors, pubmed-meshheading:11406558-Gene Expression Regulation, Enzymologic, pubmed-meshheading:11406558-Gene Expression Regulation, Neoplastic, pubmed-meshheading:11406558-Gene Silencing, pubmed-meshheading:11406558-Glutathione S-Transferase pi, pubmed-meshheading:11406558-Glutathione Transferase, pubmed-meshheading:11406558-HeLa Cells, pubmed-meshheading:11406558-Histone Deacetylase Inhibitors, pubmed-meshheading:11406558-Humans, pubmed-meshheading:11406558-Hydroxamic Acids, pubmed-meshheading:11406558-Isoenzymes, pubmed-meshheading:11406558-Male, pubmed-meshheading:11406558-Molecular Sequence Data, pubmed-meshheading:11406558-Plasmids, pubmed-meshheading:11406558-Promoter Regions, Genetic, pubmed-meshheading:11406558-Prostatic Neoplasms, pubmed-meshheading:11406558-Transfection, pubmed-meshheading:11406558-Tumor Cells, Cultured
pubmed:year
2001
pubmed:articleTitle
Cytosine methylation represses glutathione S-transferase P1 (GSTP1) gene expression in human prostate cancer cells.
pubmed:affiliation
Department of Medicine, Overton Brooks Veterans Administration Medical Center, Shreveport, Louisiana 71101-4295, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S.