Myxoid liposarcomaFUS‐DDIT3fusion oncogene induces C/EBP β‐mediated interleukin 6 expression
| Autor: | Anita Olofsson, Erik Elias, Pierre Åman, Melker Göransson, Carola Andersson, Anders Ståhlberg |
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| Rok vydání: | 2005 |
| Předmět: |
Cancer Research
Oncogene Proteins Fusion Fibrosarcoma Transplantation Heterologous Mice SCID Round Cell Liposarcoma Biology Polymerase Chain Reaction Fusion gene Mice Cell Line Tumor Gene expression CEBPB medicine Animals Humans RNA Small Interfering Promoter Regions Genetic DNA Primers Gene knockdown Myxoid liposarcoma Interleukin-6 CCAAT-Enhancer-Binding Protein-beta NF-kappa B medicine.disease Fusion protein Molecular biology Liposarcoma Myxoid Oncology CCAAT-Enhancer-Binding Proteins Cancer research RNA-Binding Protein FUS Chromatin immunoprecipitation Transcription Factor CHOP Transcription Factors |
| Zdroj: | International Journal of Cancer. 115:556-560 |
| ISSN: | 1097-0215 0020-7136 |
| DOI: | 10.1002/ijc.20893 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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