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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
22
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pubmed:dateCreated |
2002-5-28
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pubmed:abstractText |
Unregulated expression of vascular endothelial growth factor-A (VEGF-A) plays an important role in tumor growth. We have identified a cell type-specific enhancer, HS-1100, that contributes to VEGF-A transcriptional activation in tumorigenic glioblastoma cell lines. This enhancer exhibits increased accessibility to DNase I in glioblastoma cell lines that express high levels of VEGF-A but not in several other cell lines that express much lower levels of VEGF-A. HS-1100 contains a number of sequence elements that are highly conserved among human, mouse, and rat, including the hypoxia-response element (HRE). We show that the HRE contributes significantly to the cell type-specific enhancer activity of HS-1100 in U87MG glioblastoma cells. We use chromatin immunoprecipitation assays to show that endothelial PAS domain protein 1 (EPAS1) can efficiently bind to the endogenous HRE in U87MG cells but not in HEK293 cells in which the chromosomal HS-1100 is not accessible to DNase I. A dominant negative EPAS1 significantly reduces HS-1100 enhancer activity and VEGF-A levels in U87MG cells. Our results provide insight into the molecular mechanisms of VEGF-A up-regulation during cancer development.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
31
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pubmed:volume |
277
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
20087-94
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:11912213-Base Sequence,
pubmed-meshheading:11912213-Basic Helix-Loop-Helix Transcription Factors,
pubmed-meshheading:11912213-Blotting, Western,
pubmed-meshheading:11912213-Cell Line,
pubmed-meshheading:11912213-Cell Nucleus,
pubmed-meshheading:11912213-Chromatin,
pubmed-meshheading:11912213-Deoxyribonuclease I,
pubmed-meshheading:11912213-Endothelial Growth Factors,
pubmed-meshheading:11912213-Genes, Dominant,
pubmed-meshheading:11912213-Humans,
pubmed-meshheading:11912213-Luciferases,
pubmed-meshheading:11912213-Molecular Sequence Data,
pubmed-meshheading:11912213-Neuroblastoma,
pubmed-meshheading:11912213-Precipitin Tests,
pubmed-meshheading:11912213-Promoter Regions, Genetic,
pubmed-meshheading:11912213-Protein Binding,
pubmed-meshheading:11912213-RNA, Messenger,
pubmed-meshheading:11912213-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:11912213-Trans-Activators,
pubmed-meshheading:11912213-Transcription, Genetic,
pubmed-meshheading:11912213-Transfection,
pubmed-meshheading:11912213-Tumor Cells, Cultured,
pubmed-meshheading:11912213-Up-Regulation,
pubmed-meshheading:11912213-Vascular Endothelial Growth Factor A
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pubmed:year |
2002
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pubmed:articleTitle |
Activation of vascular endothelial growth factor A transcription in tumorigenic glioblastoma cell lines by an enhancer with cell type-specific DNase I accessibility.
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pubmed:affiliation |
Sangamo BioSciences Incorporated, Richmond, California 94804, USA.
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pubmed:publicationType |
Journal Article
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