The myxoid/round cell liposarcoma fusion oncogene FUS-DDIT3 and the normal DDIT3 induce a liposarcoma phenotype in transfected human fibrosarcoma cells.
Journal article, 2006
Myxoid/round cell liposarcoma (MLS/RCLS) is the most common subtype of liposarcoma. Most MLS/RCLS carry a t(12;16) translocation, resulting in a FUS-DDIT3 fusion gene. We investigated the role of the FUS-DDIT3 fusion in the development of MLS/RCLS in FUS-DDIT3- and DDIT3-transfected human HT1080 sarcoma cells. Cells expressing FUS-DDIT3 and DDIT3 grew as liposarcomas in severe combined immunodeficient mice and exhibited a capillary network morphology that was similar to networks of MLS/RCLS. Microarray-based comparison of HT1080, the transfected cells, and an MLS/RCLS-derived cell line showed that the FUS-DDIT3- and DDIT3-transfected variants shifted toward an MLS/RCLS-like expression pattern. DDIT3-transfected cells responded in vitro to adipogenic factors by accumulation of fat and transformation to a lipoblast-like morphology. In conclusion, because the fusion oncogene FUS-DDIT3 and the normal DDIT3 induce a liposarcoma phenotype when expressed in a primitive sarcoma cell line, MLS/RCLS may develop from cell types other than preadipocytes. This may explain the preferential occurrence of MLS/RCLS in nonadipose tissues. In addition, development of lipoblasts and the typical MLS/RCLS capillary network could be an effect of the DDIT3 transcription factor partner of the fusion oncogene.
metabolism
blood supply
Cluster Analysis
genetics
Up-Regulation
SCID
Fusion
Fibrosarcoma
Oncogene Proteins
metabolism
Oligonucleotide Array Sequence Analysis
Humans
Mice
metabolism
physiology
blood supply
Down-Regulation
RNA-Binding Protein FUS
physiology
metabolism
physiology
Myxoid
Neoplastic
Transcription Factor CHOP
Female
Transfection
Gene Expression Regulation
Animals
Liposarcoma
Adipogenesis
Mice
Author
Katarina Engström
University of Gothenburg
Helena Willén
Christina Kåbjörn-Gustafsson
University of Gothenburg
Carola Andersson
University of Gothenburg
Marita Olsson
Chalmers, Mathematical Sciences, Mathematical Statistics
University of Gothenburg
Melker Göransson
University of Gothenburg
Sofia Järnum
University of Gothenburg
Anita Olofsson
University of Gothenburg
Elisabet Warnhammar Finnborg
University of Gothenburg
Pierre Åman
University of Gothenburg
American Journal of Pathology
0002-9440 (ISSN) 1525-2191 (eISSN)
Vol. 168 5 1642-53Subject Categories
Cell and Molecular Biology
DOI
10.2353/ajpath.2006.050872
PubMed
16651630