The myxoid/round cell liposarcoma fusion oncogene FUS-DDIT3 and the normal DDIT3 induce a liposarcoma phenotype in transfected human fibrosarcoma cells.
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.
Engström
Katarina
K
Department of Oncology, Lundberg Laboratory for Cancer Research, Sahlgrenska University Hospital, Gothenburg, Sweden.
Willén
Helena
H
Kåbjörn-Gustafsson
Christina
C
Andersson
Carola
C
Olsson
Marita
M
Göransson
Melker
M
Järnum
Sofia
S
Olofsson
Anita
A
Warnhammar
Elisabeth
E
Aman
Pierre
P
D050156:Adipogenesis; D000818:Animals; D016000:Cluster Analysis; D015536:Down-Regulation; D005260:Female; D005354:Fibrosarcoma / Q000098:blood supply* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018208:Liposarcoma, Myxoid / Q000098:blood supply* / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D020411:Oligonucleotide Array Sequence Analysis; D015514:Oncogene Proteins, Fusion / Q000502:physiology; D034702:RNA-Binding Protein FUS / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051742:Transcription Factor CHOP / Q000378:metabolism / Q000502:physiology*; D014162:Transfection; D015854:Up-Regulation
C497249:DDIT3 protein, human; D015514:Oncogene Proteins, Fusion; D034702:RNA-Binding Protein FUS; D051742:Transcription Factor CHOP