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Myxoid liposarcoma FUS‐DDIT3 fusion oncogene induces C/EBP β‐mediated interleukin 6 expression
Author(s) -
Göransson Melker,
Elias Erik,
Ståhlberg Anders,
Olofsson Anita,
Andersson Carola,
Åman Pierre
Publication year - 2005
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.20893
Subject(s) - biology , myxoid liposarcoma , gene knockdown , microbiology and biotechnology , cancer research , cell culture , liposarcoma , genetics , medicine , pathology , sarcoma
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. © 2005 Wiley‐Liss, Inc.