Linked Life Data

21466784

Source:http://linkedlifedata.com/resource/pubmed/id/21466784

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2011-5-2
pubmed:abstractText
Elafin, a serine protease inhibitor, induces the intrinsic apoptotic pathway in human melanoma cells, where its expression is transcriptionally silenced. However, it remains unknown how the elafin gene is repressed in melanoma cells. We here demonstrate that elafin expression is modulated via epigenetically regulated expression of the transcription factor Foxa2. Treatment of melanoma cells with a DNA methyltransferase inhibitor induced elafin expression, which was specifically responsible for reduced proliferation and increased apoptosis. Suppression of Foxa2 transcription, mediated by DNA hypermethylation in its promoter region, was released in melanoma cells upon treatment with the demethylating agent. Luciferase reporter assays indicated that the Foxa2 binding site in the elafin promoter was critical for the activation of the promoter. Chromatin immunoprecipitation assays further showed that Foxa2 bound to the elafin promoter in vivo. Analyses of melanoma cells with varied levels of Foxa2 revealed a correlated expression between Foxa2 and elafin and the ability of Foxa2 to induce apoptosis. Our results collectively suggest that, in melanoma cells, Foxa2 expression is silenced and therefore elafin is maintained unexpressed to facilitate cell proliferation in the disease melanoma.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1090-2104
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
29
pubmed:volume
408
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
160-6
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Epigenetic regulation of the transcription factor Foxa2 directs differential elafin expression in melanocytes and melanoma cells.
pubmed:affiliation
Therapeutic Antibody Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, South Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't