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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
12
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pubmed:dateCreated |
2005-6-16
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pubmed:abstractText |
Meningiomas constitute the second most common central nervous system tumor, and yet relatively little is known about the molecular events that are important for the pathogenesis and malignant progression of these tumors. We have used serial analysis of gene expression to compare the transcriptomes of nonneoplastic meninges and meningiomas of all malignancy grades. A novel finding from this screen is the induction of three components of the Notch signaling pathway: the transcription factor, hairy and enhancer of Split1 (HES1) and two members of the Groucho/transducin-like enhancer of Split family of corepressors, TLE2 and TLE3. TLE corepressors interact and modulate the activity of a wide range of transcriptional regulatory systems, one of which is HES1. We have shown that the transcript and protein levels of HES1, the Notch2 and Notch1 receptors and the Jagged1 ligand are induced in meningiomas of all grades, whereas induction of TLE2 and TLE3 occurs specifically in higher-grade meningiomas. Meningioma cell lines express components of the Notch signaling pathway and an inhibitor of this pathway suppresses meningioma cell survival. These results suggest that deregulated expression of the Notch pathway is a critical event in meningioma pathogenesis and that modulation of this and potentially other signaling pathways by TLE corepressors leads to a more malignant phenotype.
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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 |
http://linkedlifedata.com/resource/pubmed/chemical/Basic Helix-Loop-Helix...,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/HES1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Homeodomain Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/NOTCH1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/NOTCH2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Notch1,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Notch2,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Serrate proteins,
http://linkedlifedata.com/resource/pubmed/chemical/TLE2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0008-5472
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
65
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5070-5
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:15958550-Basic Helix-Loop-Helix Transcription Factors,
pubmed-meshheading:15958550-Calcium-Binding Proteins,
pubmed-meshheading:15958550-Cell Line, Tumor,
pubmed-meshheading:15958550-Gene Expression Profiling,
pubmed-meshheading:15958550-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:15958550-Homeodomain Proteins,
pubmed-meshheading:15958550-Humans,
pubmed-meshheading:15958550-Intercellular Signaling Peptides and Proteins,
pubmed-meshheading:15958550-Ligands,
pubmed-meshheading:15958550-Membrane Proteins,
pubmed-meshheading:15958550-Meningeal Neoplasms,
pubmed-meshheading:15958550-Meningioma,
pubmed-meshheading:15958550-Nuclear Proteins,
pubmed-meshheading:15958550-Polymerase Chain Reaction,
pubmed-meshheading:15958550-Receptor, Notch1,
pubmed-meshheading:15958550-Receptor, Notch2,
pubmed-meshheading:15958550-Receptors, Cell Surface,
pubmed-meshheading:15958550-Repressor Proteins,
pubmed-meshheading:15958550-Signal Transduction,
pubmed-meshheading:15958550-Transcription Factors
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pubmed:year |
2005
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pubmed:articleTitle |
Meningioma transcript profiles reveal deregulated Notch signaling pathway.
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pubmed:affiliation |
Brain Tumor Research Center, Department of Neurological Surgery, University of California, San Francisco, California 94143, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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