Establishment of the method for estimation of carcinogenetic risk in gastrointestinal adenomas using double transgenic mice

双转基因小鼠胃肠道腺瘤致癌风险评估方法的建立

• 批准号: 16590487
• 负责人: HOMMA Sadamu
• 金额: $ 1.92万
• 依托单位: The Jikei University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590487/
• 关键词: APC gene; Familial Adenomatous Polyposis; Risk of carcinogenesis; LOH mutation; Model mice; Colorectal cancer; マウス

Double transgenic cells with both reporter and repressor gene should be fully functional for establishment of the method for estimation of carcinogenetic risk using double transgenic mice. For this purpose, NIH-3T3 cells transduced with both LacZ reporter gene and LacZ represser gene were established. Expression of reporter gene by treatment of the cells with Chlorambutyl, inducer of large defect mutation of chromosomes, has been examined. APC gene knockout construct including reporter gene and Smad4 knockout construct including represser gene were now being generated using genomic DNA encoding APC gene and Smad4 gene for establishment of the double transgenic mice. APC gene knockout mice with different mutation site (APC1309,APC850Min,APC580D) were examined for number of gastrointestinal tumors and accumulation of beta-catenin into cytoplasm and nucleus. It was demonstrated that mice with large number of tumors showed high accumulation of beta-catenin. However, APC1309 mice exhibiting no beta-catenin accumulation showed tumor development, suggesting that pathway without association with beta-catenin might be involved in the tumorigenesis in APC gene knockout mice.

具有报告基因和抑制剂基因的双转基因细胞应完全实现，以建立使用双转基因小鼠估算致癌风险的方法。为此，建立了用LACZ报告基因和LACZ抑制剂基因转导的NIH-3T3细胞。已经检查了通过用氯氨基丁基处理细胞的表达报告基因的诱导剂，这是染色体大缺陷突变的诱导剂。现在，使用编码APC基因和SMAD4基因的基因组DNA生成了包括抑制剂基因在内的APC基因敲除构建体，包括抑制剂基因，以建立双转基因小鼠。检查了具有不同突变位点（APC1309，APC850MIN，APC580D）的APC基因敲除小鼠的胃肠道肿瘤数量，并将β-catenin的积聚到细胞质和细胞核中。证明大量肿瘤的小鼠表现出高β-catenin的高积累。然而，没有β-catenin积累的APC1309小鼠显示出肿瘤的发育，这表明没有与β-catenin相关的途径可能与APC基因敲除小鼠的肿瘤发生有关。

项目成果

BIO Clinica

生物临床

• 发表时间: 2021
• 作者: Ikuho Sakurai;Mitsue Maru;Takako Miyamae;and Masataka Honda;櫻井育穂;櫻井育穂
• 通讯作者: 櫻井育穂

Autoimmune hepatic inflammation by vaccination of mice with dendritic cells loaded with well-differentiated hepatocellular carcinoma cells and administration of interleukin-12.

• DOI: 10.1016/j.clim.2005.08.010
• 发表时间: 2005-12
• 期刊: Clinical immunology
• 影响因子: 8.6
• 作者: Shigeo Tamaki;S. Homma;Y. Enomoto;H. Komita;M. Zeniya;T. Ohno;G. Toda

Cancer immunotherapy by fusions of dendritic and tumour cells and rhII-12.

通过树突状细胞和肿瘤细胞与 rhII-12 融合进行癌症免疫治疗。

• 发表时间: 2005
• 期刊: European Journal of Clinical Investigation 35(4)
• 作者: Yoshida;M. et al.;Karita K et al.;Sadamu Homma
• 通讯作者: Sadamu Homma

先端医療シリーズ、肝・胆・膵疾患、肝・胆・膵疾患の最新医療

先进医疗系列，肝胆胰疾病，肝胆胰疾病最新医疗护理

• 作者: Tamakoshi K;Toyoshima H;Yatsuya H.;小野雄一郎;本間 定
• 通讯作者: 本間 定

Inhibitio of spontaneous development of liver tumors by inoculation with dendritic cells loaded with hepatocellular carcinoma cells in C3H/HeNCrj mice

接种负载肝细胞癌细胞的树突状细胞可抑制 C3H/HeNCrj 小鼠肝脏肿瘤的自发发展

• 发表时间: 2004
• 期刊: International Journal of Cancer 111(2)
• 作者: Oyama T;et al.;Masaki Irie
• 通讯作者: Masaki Irie