The myxoid/round cell liposarcoma fusion oncogene FUS-DDIT3 and the normal DDIT3 induce a liposarcoma phenotype in transfected human fibrosarcoma cells.
Artikel i vetenskaplig tidskrift, 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

Författare

Katarina Engström

Göteborgs universitet

Helena Willén

Christina Kåbjörn-Gustafsson

Göteborgs universitet

Carola Andersson

Göteborgs universitet

Marita Olsson

Chalmers, Matematiska vetenskaper, matematisk statistik

Göteborgs universitet

Melker Göransson

Göteborgs universitet

Sofia Järnum

Göteborgs universitet

Anita Olofsson

Göteborgs universitet

Elisabet Warnhammar Finnborg

Göteborgs universitet

Pierre Åman

Göteborgs universitet

American Journal of Pathology

0002-9440 (ISSN) 1525-2191 (eISSN)

Vol. 168 1642-53

Ämneskategorier

Cell- och molekylärbiologi

DOI

10.2353/ajpath.2006.050872

PubMed

16651630