Comparable transforming capacities and differential gene expression patterns of variant FUS/CHOP fusion transcripts derived from soft tissue liposarcomas.
The chromosomal translocation t(12;16)(q13;p11) is a common genetic alteration in myxoid and round-cell liposarcomas. It results in transcription of various chimeric FUS/CHOP fusion transcripts that encode different oncogenic proteins. Recent reports suggest that these may have different neoplastic transformation activities. To audit this hypothesis, we transfected expression plasmids for the two major variant FUS/CHOP transcripts I and II in NIH 3T3 cells and determined the number of outgrowing foci as well as their growth potential in soft agar. In addition, we compared tumour growth in nude mice upon subcutaneous injection of the respective transfectants. No significant differences in transformation assays in vitro and in vivo were observed, suggesting that both variant transcripts confer comparable transforming activities. The histopathological picture of tumours derived from both cell populations resembles high-grade spindle cell sarcomas. This suggests that both FUS/CHOP variants cause similar patterns of differential gene expression. This hypothesis was confirmed by mRNA-expression profiles of the respective cell clones. Strong overexpression of the pentaxin-related gene (PTX), the osteoblast-specific factor 2 (osf-2), the basic Kruppel-like factor (bklf), the leucoprotease inhibitor, and the cyclophilin B were observed in both types of FUS/CHOP-transfected cell clones. Taken together, our data suggest that different FUS/CHOP variants cause transformation of mesenchymal cells via the same pathways with comparable efficacy.
Department of Surgery, University of Heidelberg, INF 110, 69120 Heidelberg, Germany.
Matthias Heinrich Martin
MH
Schwarzbach
Robert
R
Koesters
Anja
A
Germann
Gunhild
G
Mechtersheimer
Jochen
J
Geisbill
Stefanie
S
Winkler
Marco
M
Niedergethmann
Ruediger
R
Ridder
Markus W
MW
Buechler
Magnus
M
von Knebel Doeberitz
Frank
F
Willeke
D000818:Animals; D001483:Base Sequence; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D017931:DNA Primers; D005091:Exons / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D014644:Genetic Variation; D006801:Humans; D008080:Liposarcoma / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D034702:RNA-Binding Protein FUS / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012983:Soft Tissue Neoplasms / Q000235:genetics* / Q000473:pathology; D051742:Transcription Factor CHOP; D014158:Transcription, Genetic / Q000235:genetics*; D014178:Translocation, Genetic / Q000235:genetics*; D014183:Transplantation, Heterologous
D022762:CCAAT-Enhancer-Binding Proteins; D017931:DNA Primers; D015514:Oncogene Proteins, Fusion; D034702:RNA-Binding Protein FUS; C106030:TLS-CHOP fusion protein, human; D051742:Transcription Factor CHOP