Poulin Hugo, Labelle Yves
Unité de recherche en génétique humaine et moléculaire, Hôpital Saint-François d'Assise, CHUQ, Que., Canada G1L 3L5.
Cancer Lett. 2005 Sep 28;227(2):185-91. doi: 10.1016/j.canlet.2004.12.007. Epub 2005 Jan 8.
In approximately 70% of human extraskeletal myxoid chondrosarcoma (EMC) tumors, a t(9;22) chromosome translocation gives rise to a fusion protein, named EWS/NOR1, containing the amino-terminal domain of EWS fused to the complete amino acid sequence of the nuclear receptor NOR1. Several observations suggest that one role of EWS/NOR1 in EMC may be to deregulate the expression of specific genes involved in the tumoral process. In order to identify these genes, we have used a CFK2 chondrogenic cell line over-expressing EWS/NOR1. A differential display analysis has identified the PLAGL1 gene as being down-regulated in the CFK2(EWS/NOR1) cell line compared to native CFK2 cells. RT-PCR analyses show that whereas the PLAGL1 mRNAs encoding the two isoforms of the protein are highly expressed in four human chondrocyte immortalized cell lines and two human chondrocyte primary cultures, they are strongly down-regulated in six EMC tumors. We conclude that down-regulation of PLAGL1 may be a significant contributing factor in the development of EMC tumors.
在大约70%的人类骨外黏液样软骨肉瘤（EMC）肿瘤中，t(9;22)染色体易位产生一种融合蛋白，名为EWS/NOR1，它包含EWS的氨基末端结构域与核受体NOR1的完整氨基酸序列融合。多项观察结果表明，EWS/NOR1在EMC中的一个作用可能是使参与肿瘤形成过程的特定基因的表达失调。为了鉴定这些基因，我们使用了过表达EWS/NOR1的CFK2软骨生成细胞系。差异显示分析已确定PLAGL1基因在CFK2(EWS/NOR1)细胞系中相对于天然CFK2细胞下调。逆转录聚合酶链反应（RT-PCR）分析表明，虽然编码该蛋白两种异构体的PLAGL1信使核糖核酸（mRNAs）在四个人类软骨细胞永生化细胞系和两个人类软骨细胞原代培养物中高表达，但它们在六个EMC肿瘤中强烈下调。我们得出结论，PLAGL1的下调可能是EMC肿瘤发生的一个重要促成因素。
