Molecular mechanism of hepatic carcinogenesis and hepatocyte apoptosis in the Rb transgenic mice
Rb转基因小鼠肝癌发生及肝细胞凋亡的分子机制
基本信息
- 批准号:15390393
- 负责人:
- 金额:$ 9.22万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (B)
- 财政年份:2003
- 资助国家:日本
- 起止时间:2003 至 2005
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
We created the Rb transgenic mice in which the human Rb cDNA was controlled under the HNF-1 promoter/enhancer and got two lines. We determined that the A mouse had 11 copies of the transgene per haploid and the B mouse had 4 copies per haploid.We injected diethylnitrosamine into the abdominal cavity of the A mice, B mice and wild-type mice and then feed them with phenobarbital-containing water for 35 weeks. After sacrifice, the livers were examined. In the wild-type mice, several hepatocellular carcinomas were detected while no carcinomas were detected in the Rb transgenic mice, A and B mice. We extracted DNAs from the hepatocellular carcinoma in the wild-type mice and investigated the mutations of Rb,p53, Ras and Myc genes, but no mutations were detected. The number of nodules in the liver was largest in the wild-type mice, secondarily larger in the B mice and lesser in the A mice. This result indicates that Rb protein inhibits nodule formation in a dose-dependent manner.To find the molecules involved in resistance to fulminant hepatitis, firstly the cellular extracts from the livers were prepared and subjected to Western blotting. The results showed that the amounts of caspase 1, caspase 3,p53,E2F1-E2F5,Bcl-2,Bcl-XL,Bcl-XS, Bad and Bid proteins showed no differences between the wild-type and A mice. However, the Bax protein was decreased in the A mice and B mice compared to that in the wild-type mice. Second, we did 2-dimensional electrophoresis using the protein extracts from the livers in the A mice and wild-type mice. We found that 5 proteins appeared in the A mice, but not in the wild-type mice and 7 proteins disappeared in the A mice, but not in the wild-type mice.
我们建立了人Rb基因在HNF-1启动子/增强子调控下的转基因小鼠,并获得了两个品系。我们确定A小鼠每个单倍体有11个转基因拷贝,B小鼠每个单倍体有4个拷贝,我们将二乙基亚硝胺注射到A小鼠、B小鼠和野生型小鼠的腹腔中,然后用含苯巴比妥的水喂养它们35周。处死后,检查肝脏。在野生型小鼠中,检测到几种肝细胞癌,而在Rb转基因小鼠、A和B小鼠中未检测到癌。我们从野生型小鼠肝癌组织中提取DNA,检测Rb、p53、Ras和Myc基因的突变,但未检测到突变。野生型小鼠的肝脏结节数量最多,其次是B小鼠,A小鼠较少。这一结果表明Rb蛋白以剂量依赖的方式抑制结节的形成。为了寻找参与抵抗暴发性肝炎的分子,首先制备了来自肝脏的细胞提取物并进行了Western印迹。结果表明,caspase 1、caspase 3、p53、E2 F1-E2 F5、Bcl-2、Bcl-XL、Bcl-XS、Bad和Bid蛋白的表达量在野生型小鼠和A小鼠之间没有差异。然而,与野生型小鼠相比,Bax蛋白在A小鼠和B小鼠中减少。第二,我们使用A小鼠和野生型小鼠肝脏的蛋白质提取物进行二维电泳。我们发现有5种蛋白质在A小鼠中出现,但在野生型小鼠中没有,7种蛋白质在A小鼠中消失,但在野生型小鼠中没有。
项目成果
期刊论文数量(12)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
FOXC2 haploinsufficient mice are a model for human autosomal dominant lymphedema-distichiasis syndrome
- DOI:10.1093/hmg/ddg123
- 发表时间:2003-05-15
- 期刊:
- 影响因子:3.5
- 作者:Kriederman, BM;Myloyde, TL;Glover, TW
- 通讯作者:Glover, TW
Neurogenesin-1 differentially inhibits the osteoblastic differentiation by bone morphogenetic proteins in C2C12 cells
- DOI:10.1016/j.bbrc.2006.03.195
- 发表时间:2006-06-09
- 期刊:
- 影响因子:3.1
- 作者:Chandra, Abhshek;Itakura, Tatsuo;Miura, Naoyuki
- 通讯作者:Miura, Naoyuki
FOXC2遺伝子と先天性リンパ水腫
FOXC2基因与先天性淋巴水肿
- DOI:
- 发表时间:2004
- 期刊:
- 影响因子:0
- 作者:本橋 豊;金子善博;本橋 豊;三浦直行;Yutaka Motohashi et al.;三浦直行
- 通讯作者:三浦直行
Kriederman, B.M.: "FOXC2 haploinsufficient mice are a model for human autosomal dominant lymphedema-distichiasis syndrome."Hum.Mol.Genet.. 12. 1179-1185 (2003)
Kriederman, B.M.:“FOXC2 单倍体不足的小鼠是人类常染色体显性淋巴水肿-双裂综合征的模型。”Hum.Mol.Genet.. 12. 1179-1185 (2003)
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Defective valves and abnormal mural cell recruitment as a mechanism for the lymphatic vascular failure in lymphedema-distichiasis.
有缺陷的瓣膜和异常的壁细胞募集是淋巴水肿-双歧病中淋巴管衰竭的机制。
- DOI:
- 发表时间:2004
- 期刊:
- 影响因子:0
- 作者:Petrova;T.V. et al.
- 通讯作者:T.V. et al.
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MIURA Naoyuki其他文献
MIURA Naoyuki的其他文献
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{{ truncateString('MIURA Naoyuki', 18)}}的其他基金
Generation of the HCV-infectable mouse-an animal model for inflammation cancer
HCV感染小鼠的产生——炎症性癌症动物模型
- 批准号:
24659603 - 财政年份:2012
- 资助金额:
$ 9.22万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
Generation of mice in which the mouse hepatocytes are replaced with the human hepaocytes and its application
人肝细胞替代小鼠肝细胞的小鼠产生及其应用
- 批准号:
19390347 - 财政年份:2007
- 资助金额:
$ 9.22万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Molecular machanism of the MFH-1 gene in, the aoortic arch formation, Skeletogenesis and kidney formation
MFH-1基因在主动脉弓形成、骨骼发生和肾脏形成中的分子机制
- 批准号:
11694239 - 财政年份:1999
- 资助金额:
$ 9.22万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Molecular investigation on the hepatic caicinogenesis-resistant model animals
肝脏抗癌模型动物的分子研究
- 批准号:
11557090 - 财政年份:1999
- 资助金额:
$ 9.22万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Molecular investigation on the fulminant hepatitis-resistant model animals
暴发性肝炎耐药模型动物的分子研究
- 批准号:
10470253 - 财政年份:1998
- 资助金额:
$ 9.22万 - 项目类别:
Grant-in-Aid for Scientific Research (B).
ROLES OF THE MFH-1 AND WT1 GENES IN KIDNEY DEVELOPMENT
MFH-1 和 WT1 基因在肾脏发育中的作用
- 批准号:
09044252 - 财政年份:1997
- 资助金额:
$ 9.22万 - 项目类别:
Grant-in-Aid for international Scientific Research
Roles of the MFH-1 gene and WT 1 gene in kidney development
MFH-1 基因和 WT 1 基因在肾脏发育中的作用
- 批准号:
08044238 - 财政年份:1996
- 资助金额:
$ 9.22万 - 项目类别:
Grant-in-Aid for international Scientific Research
GENERATION AND APPLICATION OF THE MODEL MICE WHICH SHOW RESISTANCE TO RENAL CARCINOGENESIS
抗肾癌小鼠模型的产生及应用
- 批准号:
08557089 - 财政年份:1996
- 资助金额:
$ 9.22万 - 项目类别:
Grant-in-Aid for Scientific Research (A)
Lsolation and characterization of the Brain Forkhead gene
脑叉头基因的分离和表征
- 批准号:
05680592 - 财政年份:1993
- 资助金额:
$ 9.22万 - 项目类别:
Grant-in-Aid for General Scientific Research (C)
Molecular Cloning of Rat Hepatocyte Nuclear Factor 1 Gene and Analysis of Its Promotor
大鼠肝细胞核因子1基因的分子克隆及其启动子分析
- 批准号:
02670108 - 财政年份:1990
- 资助金额:
$ 9.22万 - 项目类别:
Grant-in-Aid for General Scientific Research (C)