EWS/FLI function varies in different cellular backgrounds
EWS/FLI function varies in different cellular backgrounds
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DOI：
10.1016/s0014-4827(03)00371-9
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发表时间：
2003-11-01
影响因子：
3.7
通讯作者：
May, WA
中科院分区：
文献类型：
--
作者：
Zwerner, JP;Guimbellot, J;May, WA
EWS/FLI和其他EWS/ets嵌合转录因子在尤文家族肿瘤的生物学中起着核心作用。与许多癌基因一样，EWS/FLI生物活性可以在有限的细胞环境中得到证实。为了研究这种限制的原因，我们证明了两个永生化的成纤维细胞系对EWS/FLI转化具有抗性，Rat 1和Yal 7，表达稳定水平的EWS/FLI蛋白。尽管Rat 1和Ya 17对EWS/FLI具有抗性，但它们可以被有效的EWS/FLI下游介导物PDGF-C转化。与NIH 3 T3相反，EWS/FLI抗性系不显示PDGF-C响应于EWS/FLI的上调，证明了不同细胞背景中的不同EWS/FLI功能。EWS/FLI的其他几个NIH 3 T3靶标也可以证明这种差异功能现象。尽管锚定非依赖性生长和PDGF-C诱导之间存在相关性，但PDGF-C在N1 H3 T3细胞中不能完全再现EWS/FLI表型的所有方面。这些结果进一步指出了PDGF-C在介导EWS/FLI体外转化中的重要性，并建议谨慎假设转录因子在不同的细胞背景中产生相同的作用。(C)2003年爱思唯尔公司All rights reserved.
EWS/FLI and other EWS/ets chimeric transcription factors play a central role in the biology of the Ewing family tumors. As with many oncogenes, EWS/FLI biologic activity can be demonstrated in a limited range of cellular contexts. To investigate the causes of this restriction, we demonstrate that two immortalized fibroblast lines resistant to EWS/FLI transformation, Rat1 and Yal7, express stable levels of EWS/FLI protein. Despite their resistance to EWS/FLI, Rat1 and Ya17 can be transformed by the potent EWS/FLI downstream mediator PDGF-C. In contrast to NIH3T3, the EWS/FLI resistant lines show no upregulation of PDGF-C in response to EWS/FLI, demonstrating differential EWS/FLI function in different cellular backgrounds. This phenomenon of differential function can also be demonstrated for several other NIH3T3 targets of EWS/FLI. Despite the correlation between anchorage-independent growth and PDGF-C induction, PDGF-C does not fully reproduce all aspects of the EWS/FLI phenotype in N1H3T3 cells. These results further point to the importance of PDGF-C in mediating EWS/FLI in vitro transformation and suggest caution in assuming that a transcription factor will produce identical effects in different cellular backgrounds. (C) 2003 Elsevier Inc. All rights reserved.