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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
15
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pubmed:dateCreated |
2008-4-3
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pubmed:abstractText |
The protooncogene c-met encodes the tyrosine kinase receptor for the hepatocyte growth factor/scatter factor (HGF/SF). While overexpression of c-met is documented in many types of tumors, the mechanism of c-met regulation remains elusive. Here, we demonstrate Daxx as a repressor of c-met transcription. The expression of c-met is elevated in Daxx knockout mouse cells and is reversed by Daxx reconstitution. C-met promoter analysis of Daxx-/- cells reveled changes in chromatin acetylation, but not in DNA methylation. Daxx binds to the mouse c-met promoter and Daxx-binding region is sufficient for transcription repression, while HDAC2 is associated with c-met promoter mostly in Daxx+/+ cells, pointing to Daxx-dependent HDAC2 recruitment as a potential mechanism of c-met repression. HGF-induced cell mobility and invasion confirmed augmented activity of c-Met/HGF pathway in Daxx-/- cells. Finally, inverse correlation between Daxx and c-Met in cancer cell lines and in metastatic breast cancer specimens suggests potential function of Daxx as a c-met repressor during cancer progression.
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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/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Chromatin,
http://linkedlifedata.com/resource/pubmed/chemical/Daxx protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Hdac2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Histone Deacetylase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Histone Deacetylases,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-met,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1476-5594
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
3
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pubmed:volume |
27
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2177-86
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:17952115-Animals,
pubmed-meshheading:17952115-Breast Neoplasms,
pubmed-meshheading:17952115-Carcinoma,
pubmed-meshheading:17952115-Carrier Proteins,
pubmed-meshheading:17952115-Cell Movement,
pubmed-meshheading:17952115-Chromatin,
pubmed-meshheading:17952115-DNA Methylation,
pubmed-meshheading:17952115-Disease Progression,
pubmed-meshheading:17952115-Down-Regulation,
pubmed-meshheading:17952115-Gene Expression Regulation,
pubmed-meshheading:17952115-Histone Deacetylase 2,
pubmed-meshheading:17952115-Histone Deacetylases,
pubmed-meshheading:17952115-Humans,
pubmed-meshheading:17952115-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:17952115-Mice,
pubmed-meshheading:17952115-Mice, Knockout,
pubmed-meshheading:17952115-Nuclear Proteins,
pubmed-meshheading:17952115-Promoter Regions, Genetic,
pubmed-meshheading:17952115-Protein Binding,
pubmed-meshheading:17952115-Proto-Oncogene Proteins c-met,
pubmed-meshheading:17952115-Repressor Proteins,
pubmed-meshheading:17952115-Sequence Deletion,
pubmed-meshheading:17952115-Tumor Cells, Cultured,
pubmed-meshheading:17952115-Wound Healing
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pubmed:year |
2008
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pubmed:articleTitle |
Regulation of c-met expression by transcription repressor Daxx.
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pubmed:affiliation |
Department of Anatomy & Cell Biology and Shands Cancer Center, University of Florida, Gainesville, FL, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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