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Myxoid liposarcoma FUS-DDIT3 fusion oncogene induces C/EBP β-mediated interleukin 6 expression

Melker Göransson ; Erik Elias ; Anders Ståhlberg (Institutionen för kemi- och bioteknik) ; Anita Olofsson ; Carola Andersson ; Pierre Åman
International Journal of Cancer (0020-7136). Vol. 115 (2005), 4, p. 556-560.
[Artikel, refereegranskad vetenskaplig]

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 flbrosarcoma 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 β and NFκB.

Nyckelord: MLS/RCLS; FUS; DDIT3; CEBP β; NFκB

Denna post skapades 2010-01-27. Senast ändrad 2012-08-21.
CPL Pubid: 111034


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Institutioner (Chalmers)

Institutionen för laboratoriemedicin , Avdelningen för patologi (1991-2005)
Institutionen för kemi- och bioteknik (2005-2014)



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