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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2005-4-25
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pubmed:abstractText |
The myxoid/round cell liposarcoma oncogene FUS-DDIT3 is the result of a translocation derived gene fusion between the splicing factor FUS and DDIT3. In order to investigate the downstream targets of DDIT3, and the transforming effects of the FUS-DDIT3 fusion protein, we have introduced DDIT3-GFP and FUS-DDIT3-GFP constructs into a human fibrosarcoma cell line. The gene expression profiles of stable transfectants were compared to the original fibrosarcoma cell line by microarray analysis. We here report that the NFkappaB and C/EBP beta controlled gene IL6 is upregulated in DDIT3- and FUS-DDIT3-expressing fibrosarcoma cell lines and in myxoid liposarcoma cell lines. Strong expression of the tumor associated multifunctional cytokine interleukin 6 was confirmed both at mRNA and protein level. Knockdown experiments using siRNA against CEBPB transcripts showed that the effect of FUS-DDIT3 on IL6 expression is C/EBP beta dependent. Chromatin immunoprecipitation revealed direct interaction between the IL6 promoter and the C/EBP beta protein. In addition, the effect of DDIT3 and FUS-DDIT3 on the expression of other acute phase genes was examined using real-time PCR. We demonstrate for the first time that DDIT3 and FUS-DDIT3 show opposite transcriptional regulation of IL8 and suggest that FUS-DDIT3 may affect the synergistic activation of promoters regulated by C/EBP beta and NFkappaB.
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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/CCAAT-Enhancer-Binding Protein-beta,
http://linkedlifedata.com/resource/pubmed/chemical/CCAAT-Enhancer-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DDIT3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Primers,
http://linkedlifedata.com/resource/pubmed/chemical/Ddit3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Oncogene Proteins, Fusion,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/RNA-Binding Protein FUS,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor CHOP,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0020-7136
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pubmed:author |
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pubmed:copyrightInfo |
Copyright 2005 Wiley-Liss, Inc.
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
115
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
556-60
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:15688424-Animals,
pubmed-meshheading:15688424-CCAAT-Enhancer-Binding Protein-beta,
pubmed-meshheading:15688424-CCAAT-Enhancer-Binding Proteins,
pubmed-meshheading:15688424-Cell Line, Tumor,
pubmed-meshheading:15688424-DNA Primers,
pubmed-meshheading:15688424-Fibrosarcoma,
pubmed-meshheading:15688424-Humans,
pubmed-meshheading:15688424-Interleukin-6,
pubmed-meshheading:15688424-Liposarcoma, Myxoid,
pubmed-meshheading:15688424-Mice,
pubmed-meshheading:15688424-Mice, SCID,
pubmed-meshheading:15688424-NF-kappa B,
pubmed-meshheading:15688424-Oncogene Proteins, Fusion,
pubmed-meshheading:15688424-Polymerase Chain Reaction,
pubmed-meshheading:15688424-Promoter Regions, Genetic,
pubmed-meshheading:15688424-RNA, Small Interfering,
pubmed-meshheading:15688424-RNA-Binding Protein FUS,
pubmed-meshheading:15688424-Transcription Factor CHOP,
pubmed-meshheading:15688424-Transcription Factors,
pubmed-meshheading:15688424-Transplantation, Heterologous
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pubmed:year |
2005
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pubmed:articleTitle |
Myxoid liposarcoma FUS-DDIT3 fusion oncogene induces C/EBP beta-mediated interleukin 6 expression.
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pubmed:affiliation |
Lundberg Laboratory for Cancer Research (LLCR), Department of Pathology, Goteborg University, Gothenburg, Sweden. melker.goransson@llcr.med.gu.se
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pubmed:publicationType |
Journal Article
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