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.

本研究的目的是在尤因肉瘤发生的母体组织中表达癌基因，并分离实验小鼠模型。进一步，确定EWS-FLI融合转录因子控制的靶基因。我们分离了两株携带EWS-FLI癌基因的转基因小鼠。这些小鼠具有生殖潜能，能够在正常条件下繁殖。我们将这些小鼠与神经嵴表达Cre酶的实验小鼠杂交。这使我们能够在体内诱导DNA重组，并在神经嵴源性细胞中激活EWS-FLI致癌基因。由于获得的小鼠数量不够，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，并与Cre转基因小鼠再次杂交。在我们引入致癌基因EWS-FLI的细胞系中，我们发现该基因的表达发生了显著改变。通过cDNA阵列分析，我们发现EWS-FLI激活了细胞外基质成分tenascin基因。我们还发现一个融合转录因子激活了与细胞永生相关的端粒酶基因。我们将继续制作Ewing肉瘤模型实验小鼠，并将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)。

Induction of tenascin‐C by tumor‐specific EWS‐ETS fusion genes

• DOI: 10.1002/gcc.10153
• 发表时间: 2003-03
• 期刊: Genes
• 影响因子: 3.5
• 作者: G. Watanabe;H. Nishimori;H. Irifune;Y. Sasaki;S. Ishida;H. Zembutsu;Toshihiro Tanaka;S. Kawaguchi;T. Wada;J. Hata;M. Kusakabe;Koichi Yoshida;Yusuke Nakamura;T. Tokino

E1AF/PEA3 reduces the invasiveness of SiHa cervical cancer cells by activating serine proteinase inhibitor squamous cell carcinoma antigen.

E1AF/PEA3通过激活丝氨酸蛋白酶抑制剂鳞状细胞癌抗原来降低SiHa宫颈癌细胞的侵袭性。

• 发表时间: 2004
• 期刊: Exp.Cell Res. 299
• 作者: Iwasaki;M.
• 通讯作者: M.

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

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。