Myxoid liposarcoma FUS‐DDIT3 fusion oncogene induces C/EBP β‐mediated interleukin 6 expression
Open Access
- 18 April 2005
- journal article
- research article
- Published by Wiley in International Journal of Cancer
- Vol. 115 (4), 556-560
- https://doi.org/10.1002/ijc.20893
Abstract
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 NFκB and C/EBP β 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 β dependent. Chromatin immunoprecipitation revealed direct interaction between the IL6 promoter and the C/EBP β 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 βκB.Keywords
Funding Information
- Inga-Britt and Arne Lundberg Research Foundation
- Swedish Cancer Society
- The King Gustav V Jubilée Clinic Cancer Research Foundation
- Assar Gabrielssons Research Foundation
- Johan Jansson Foundation for Cancer Research
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