Owen Leah A, Lessnick Stephen L
The Department of Oncological Sciences, University of Utah School of Medicine, Salt Lake City, Utah, USA.
Cell Cycle. 2006 Sep;5(18):2049-53. doi: 10.4161/cc.5.18.3213. Epub 2006 Sep 15.
Ewing's sarcoma is the second most common tumor of bone in children and young adults, and requires highly intensive chemotherapy along with surgery and/or radiation for successful treatment. Because these therapies are associated with significant short- and long-term side effects, new therapeutic approaches are needed. Most cases of Ewing's sarcoma contain somatic translocations between chromosomes 11 and 22 that result in the t(11;22)(q24;q12). This translocation encodes the EWS/FLI fusion protein. EWS/FLI formation appears to be the critical oncogenic event in the development of Ewing's sarcoma. It is hoped that an in-depth understanding of the mechanism that EWS/FLI uses to cause oncogenic transformation will result in new therapies for this disease. Unfortunately, this hope has not been realized. One difficulty has been the lack of an appropriate model system in which to study the fusion oncoprotein. We recently described and validated the use of retroviral RNA interference approaches to study EWS/FLI in Ewing's sarcoma cell lines. We now put this model into a historical context, and describe the benefits (both perceived and observed) of this model over previous approaches using heterologous cell types.
尤因肉瘤是儿童和青年中第二常见的骨肿瘤，成功治疗需要强化化疗以及手术和/或放疗。由于这些疗法会带来显著的短期和长期副作用，因此需要新的治疗方法。大多数尤因肉瘤病例存在11号和22号染色体之间的体细胞易位，导致t(11;22)(q24;q12)。这种易位编码EWS/FLI融合蛋白。EWS/FLI的形成似乎是尤因肉瘤发生发展中的关键致癌事件。希望深入了解EWS/FLI导致致癌转化的机制能为这种疾病带来新的治疗方法。不幸的是，这一希望尚未实现。一个困难是缺乏合适的模型系统来研究融合癌蛋白。我们最近描述并验证了使用逆转录病毒RNA干扰方法在尤因肉瘤细胞系中研究EWS/FLI。我们现在将这个模型置于历史背景中，并描述该模型相对于以往使用异源细胞类型的方法所具有的优势（包括感知到的和观察到的）。
