Analysis of Ewing sarcoma using a transgenic mouse

本研究的一个目的是在尤文肉瘤发生的母组织中表达癌基因，并分离实验室小鼠模型。此外，还鉴定EWS-FLI融合转录因子控制的靶基因。我们分离到一只携带EWS-FLI癌基因的两个品系转基因小鼠。这些小鼠具有生殖潜力，能够在正常条件下繁殖。我们将这些小鼠与在神经嵴中表达Cre酶的实验室小鼠杂交。这使我们能够在体内诱导DNA重组和EWS-FLI癌基因在神经嵴来源的细胞中的激活。由于没有获得足够数量的小鼠，我们无法判断肉瘤的发生。我们将分离出一种不同的转基因小鼠品系，并再次将其与Cre转基因小鼠杂交。在我们导入癌基因EWS-FLI的细胞系中，我们发现表达显著改变的基因。我们明确了cDNA阵列方法，tenascin基因，细胞外基质成分，被激活EWS-FLI。我们还发现一种融合转录因子激活了与细胞永生化相关的端粒酶基因。我们继续制造尤因肉瘤的实验室小鼠模型，并将研究靶基因在肿瘤发展中的作用。

A goal of this study is to express the oncogene in mother tissue for Ewing sarcoma-genesis and to isolate a model laboratory mouse. Furthermore, it is to identify a target gene which the EWS-FLI fusion transcription factor controls. We isolated a transgenic mouse of two strains carrying EWS-FLI oncogene. These mice had reproductive potential and were able to propagate in a normal condition. We crossbred these mice with the laboratory mouse which expresses Cre enzyme in neural crest. This allows us to induce a recombination of DNA in vivo and an activation of EWS-FLI oncogene in neural crest-derived cells. Since mouse was not obtained in enough numbers, we were unable to judge sarcoma-genesis. We are going to isolate a different strain of transgenic mouse and crossbreed it with the Cre transgenic mouse again. In the cell line which we introduced the oncogene EWS-FLI into, we found the gene which expression was significantly altered. We made clear by cDNA array method that the tenascin gene, an extra-cellular matrix component, was activated by EWS-FLI. Also we found that a fusion transcription factor activated telomerase gene which is associated with cellular immortalization. We continue manufacture of model laboratory mouse of Ewing sarcoma and are going to examine a role of target gene in development of the neoplasm.