Analysis of Ewing sarcoma using a transgenic mouse

使用转基因小鼠分析尤文肉瘤

• 批准号: 15591593
• 负责人: YOSHIDA Koichi
• 金额: $ 2.37万
• 依托单位: Sapporo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591593/
• 关键词: Ewing sarcoma; mouse model of disease; fusion oncogene; EWS-FLI; cre-loxP; chromosome translocation; telomerase; ETS transcription factor; 標的遺伝子; トランスジェニックマウス; Cre-loxP DNA組み換え; PNET; 肉腫; EWS; ETS

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.

本研究的目标是在母体组织中表达尤文肉瘤发生的癌基因，并分离模型实验室小鼠。此外，还鉴定EWS-FLI融合转录因子控制的靶基因。我们分离出了携带 EWS-FLI 癌基因的两种品系的转基因小鼠。这些小鼠具有繁殖潜力并且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，并在神经嵴衍生细胞中诱导 EWS-FLI 癌基因的激活。由于小鼠数量不足，我们无法判断肉瘤的发生。我们将分离出一种不同品系的转基因小鼠，并将其与Cre转基因小鼠再次杂交。在我们引入癌基因EWS-FLI的细胞系中，我们发现该基因的表达发生了显着改变。我们通过cDNA阵列方法明确了EWS-FLI激活了细胞外基质成分生腱蛋白基因。我们还发现融合转录因子激活了与细胞永生化相关的端粒酶基因。我们继续制造尤文肉瘤模型实验小鼠，并研究靶基因在肿瘤发展中的作用。

项目成果

Emi Ito: "A tetraspanin-family protein, T-cell acute lymphoblastic leukemia-associated Antigen 1, is induced by the Ewing's sarcoma-Wilms' Tumor 1"American Journal of Pathology. 163・6. 2165-2172 (2003)

Emi Ito：“四跨膜蛋白家族蛋白，T 细胞急性淋巴细胞白血病相关抗原 1，由尤文氏肉瘤 - 维尔姆斯肿瘤 1 诱导”美国病理学杂志 163·6 (2003)。

Akiko Takahashi: "EWS/ETS fusions activate teromerase in Ewing's tumors"Cancer Research. 63. 8338-8344 (2003)

Akiko Takahashi：“EWS/ETS 融合激活尤文氏肿瘤中的端粒酶”癌症研究。

EWS/ETS fusions activate teromerase in Ewing's tumors

EWS/ETS 融合激活尤文氏肿瘤中的端粒酶

• 发表时间: 2003
• 期刊: Cancer Research 63
• 作者: Iwasaki M;Nishikawa A;Akutagawa N;Fujimoyo T;Teramoto M;Sakaguchi Y;Kato H;Ito M;Yoshida K;Kudo R.;Akiko Takahashi
• 通讯作者: Akiko Takahashi

E1AF expression is closely correlated with malignant phenotype of tongue squamous cell carcinoma through activation of MT1-MMP gene promoters.

E1AF表达通过MT1-MMP基因启动子的激活与舌鳞状细胞癌的恶性表型密切相关。

• 发表时间: 2005
• 期刊: Oncology Report 13
• 作者: Akiko Takahashi;Y Izumiyama
• 通讯作者: Y Izumiyama

A tetraspanin-family protein, T-cell acute lymphoblastic leuhemia-associated antigen, is induced by the Ewing's sarcoma-Wilms'tumor 1 fusion protein of desmoplastic small round cell tumor

四跨膜蛋白家族蛋白，T 细胞急性淋巴细胞白血病相关抗原，由促结缔组织增生性小圆细胞肿瘤的尤文肉瘤-维尔姆斯肿瘤 1 融合蛋白诱导

• 发表时间: 2003
• 期刊: Am J Pathol 163
• 作者: Ito E;Honma R;Imai J-I;Azuma S;Kanno T;Mori S;Yoshie O;Nishio J;Iwasaki H;Yoshida K;Gohda J;Inoue J-I;Watanabe S;Semba K.
• 通讯作者: Semba K.