Filion Christine, Labelle Yves
Human and Molecular Genetic Research Unit, Pavillon Saint-François d'Assise, CHUQ, Quebec, Qc, Canada G1L 3L5.
Exp Cell Res. 2004 Jul 15;297(2):585-92. doi: 10.1016/j.yexcr.2004.03.040.
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.
EWS/NOR-1融合蛋白由t(9;22)染色体易位编码，约75%的骨外黏液样软骨肉瘤（EMC）肿瘤中可发现这种易位。缺乏能表达这种融合蛋白致癌特性的细胞模型严重阻碍了对其在EMC发生发展中作用的研究。为了构建这样一个细胞模型，我们使用了软骨生成细胞系CFK2。我们在本研究中表明，虽然EWS/NOR-1的稳定表达不会改变亚汇合培养中CFK2细胞的群体倍增时间和细胞周期分布，但通过汇合后生长和在软琼脂糖培养基中不依赖贴壁生长来衡量，它会诱导细胞转化。CFK2(EWS/NOR-1)细胞系中糖胺聚糖的积累表明，融合蛋白似乎不干扰CFK2细胞在体外分化为软骨样细胞的能力。这些结果支持了以下假设：EWS/NOR-1在EMC中的作用可能是破坏参与软骨生成的细胞的增殖特性。
