Source:http://linkedlifedata.com/resource/pubmed/id/16007202
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
41
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pubmed:dateCreated |
2005-9-15
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pubmed:abstractText |
Three distinct proliferative signals for multiple myeloma (MM) cell lines induce enhancer of zeste homolog 2 (ezh 2) transcript expression. EZH 2 is a polycomb group protein that mediates repression of gene transcription at the chromatin level through its methyltransferase activity. Normal bone marrow plasma cells do not express ezh2; however, gene expression is induced and correlates with tumor burden during progression of this disease. We therefore investigated how EZH 2 expression is deregulated in MM cell lines and determined the consequence of this activity on proliferation and transformation. We found that EZH 2 protein expression is induced by interleukin 6 (IL-6) in growth factor-dependent cell lines and is constitutive in IL-6-independent cell lines. Furthermore, EZH 2 expression correlates with proliferation and B-cell terminal differentiation. Significantly, EZH 2 protein inhibition by short interference RNA treatment results in MM cell growth arrest. Conversely, EZH 2 ectopic overexpression induces growth factor independence. We found that the growth factor-independent proliferative phenotype in MM cell lines harboring a mutant N- or K-ras gene requires EZH 2 activity. Finally, this is the first report to demonstrate that EZH 2 has oncogenic activity in vivo, and that cell transformation and tumor formation require histone methyltransferase activity.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0950-9232
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pubmed:author | |
pubmed:copyrightInfo |
Oncogene (2005) 24, 6269-6280.
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
24
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6269-80
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:16007202-Animals,
pubmed-meshheading:16007202-Catalysis,
pubmed-meshheading:16007202-Cell Differentiation,
pubmed-meshheading:16007202-Cell Division,
pubmed-meshheading:16007202-Cell Proliferation,
pubmed-meshheading:16007202-DNA-Binding Proteins,
pubmed-meshheading:16007202-Genes, ras,
pubmed-meshheading:16007202-Humans,
pubmed-meshheading:16007202-Interleukin-6,
pubmed-meshheading:16007202-Mice,
pubmed-meshheading:16007202-Mice, Inbred BALB C,
pubmed-meshheading:16007202-Mice, Nude,
pubmed-meshheading:16007202-Multiple Myeloma,
pubmed-meshheading:16007202-Mutation,
pubmed-meshheading:16007202-NIH 3T3 Cells,
pubmed-meshheading:16007202-Phenotype,
pubmed-meshheading:16007202-Transcription Factors
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pubmed:year |
2005
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pubmed:articleTitle |
The polycomb group protein enhancer of zeste homolog 2 (EZH 2) is an oncogene that influences myeloma cell growth and the mutant ras phenotype.
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pubmed:affiliation |
The Graduate Program in Molecular, Cellular, Developmental Biology, and Genetics, University of Minnesota, Minneapolis, MN 55455, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, N.I.H., Extramural
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