The oncogenic fusion protein EWS/NOR-1 induces transformation of CFK2 chondrogenic cells.
The EWS/NOR-1 fusion protein is encoded by the t(9;22) chromosomal translocation found in approximately 75% of extraskeletal myxoid chondrosarcoma (EMC) tumors. The lack of cellular models in which the oncogenic properties of this fusion protein are expressed has seriously hampered the study of its role in the development of EMC. To generate such a cellular model, we have used the chondrogenic cell line CFK2. We show in this study that although stable expression of EWS/NOR-1 does not alter the population doubling time and the cell cycle distribution of CFK2 cells in subconfluent cultures, it induces their transformation as measured by growth beyond confluency and anchorage-independent growth in soft agarose medium. Glycosaminoglycan accumulation in CFK2(EWS/NOR-1) cell lines indicate that the fusion protein does not appear to interfere with the ability of CFK2 cells to differentiate into chondrocyte-like cells in vitro. These results support the hypothesis that the role of EWS/NOR-1 in EMC may be to disrupt the proliferation properties of cells involved in chondrogenesis.
Filion
Christine
C
Human and Molecular Genetic Research Unit, Pavillon Saint-François d'Assise, CHUQ, Quebec, Qc, Canada G1L 3L5.
Labelle
Yves
Y
D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D019902:Chondrocytes / Q000166:cytology*; D002892:Chromosomes, Human, Pair 22; D002899:Chromosomes, Human, Pair 9; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000096:biosynthesis; D006801:Humans; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015514:Oncogene Proteins, Fusion / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D051381:Rats; D011987:Receptors, Steroid; D011988:Receptors, Thyroid Hormone; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012512:Sarcoma, Ewing / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014178:Translocation, Genetic
D004268:DNA-Binding Proteins; D006025:Glycosaminoglycans; C490412:NR4A3 protein, human; D009419:Nerve Tissue Proteins; C091333:Nr4a3 protein, rat; D015514:Oncogene Proteins, Fusion; D011987:Receptors, Steroid; D011988:Receptors, Thyroid Hormone