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

Göransson, Melker, 1974 (författare): Gothenburg University,Göteborgs universitet,Institutionen för laboratoriemedicin , Avdelningen för patologi,Institute of Laboratory Medicine, Dept of Pathology

Elias, Erik, 1979 (författare): Gothenburg University,Göteborgs universitet,Institutionen för laboratoriemedicin , Avdelningen för patologi,Institute of Laboratory Medicine, Dept of Pathology

Ståhlberg, Anders, 1975 (författare): Chalmers tekniska högskola,Chalmers University of Technology

Olofsson, Anita, 1943 (författare): Gothenburg University,Göteborgs universitet,Institutionen för laboratoriemedicin , Avdelningen för patologi,Institute of Laboratory Medicine, Dept of Pathology

Andersson, Carola, 1972 (författare): Gothenburg University,Göteborgs universitet,Institutionen för laboratoriemedicin , Avdelningen för patologi,Institute of Laboratory Medicine, Dept of Pathology

Åman, Pierre, 1953 (författare): Gothenburg University,Göteborgs universitet,Institutionen för laboratoriemedicin , Avdelningen för patologi,Institute of Laboratory Medicine, Dept of Pathology

(creator_code:org_t)

2005-04-18
2005
Engelska.
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 115:4, s. 556-560

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Abstract Ämnesord

Stäng

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.

Av författaren/redakt...: Göransson, Melke ...; Elias, Erik, 197 ...; Ståhlberg, Ander ...; Olofsson, Anita, ...; Andersson, Carol ...; Åman, Pierre, 19 ...

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