Molecular mechanism of hypercarcinogenic state -inflammation-induced hepatocarcinogenesis-
高致癌状态的分子机制-炎症诱导肝癌发生-
基本信息
- 批准号:16390121
- 负责人:
- 金额:$ 9.54万
- 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:2004
- 资助国家:日本
- 起止时间:2004 至 2005
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Cancer is a heritable disorder of somatic cells. Carcinogenesis looks like an opened Japanese fan, because initiated cells grow in several directions and tumors suggest the edge of the fan having many gene abnormalities.Development of hepatocellular carcinoma (HCC) is associated with the chronic inflammation of the liver caused by various factors such as hepatitis B or C virus infection. We reported DNA binding protein A (dbpA) as a candidate molecule that can accelerate the inflammation-induced hepatocarcinogenesis DbpA belongs to the Y box binding protein family, and YB-1, the prototype member of this family, is reported to be a prognostic marker of malignant diseases other than HCC. The purpose of this study was to examine the significance of the expression of dbpA, or of the T to G transversion in the dbpA promoter region which enhances the promoter activity in vitro, for the progression of HCC.(1)The dbpA expression was associated with the advanced stages of HCC, and the cases wit … More h the nuclear dbpA expression had a poor prognosis.(2)DbpA contributed more significantly to this association than YB-1.(3)The T to G transversion in the dbpA promoter region was related to the nuclear localization of dbpA.We reported that dbpA transcription is positively regulated by E2F1 which is also implicated in hepatocarcinogenesis. To study the in vivo effect of dbpA on the hepatocarcinogenesis, we generated the dbpA-transgenic mouse that specifically expressed a transgene in hepatocytes. We studied the effect of dbpA on the expression of other cellular genes by using microarray analyses. The expression profiles from livers of 31 and 32 week-old male transgenic mice (Tg (+)) that did not show any morphological changes and from livers of their male wild-type littermates (Tg (-)) were compared.(4)The 11 up-regulated genes included 7 carcinogenesis-related genes (Igfbp1, Tff3, Hpx, Orm2, Cts1, Plg, Jdp1), and the 9 down-regulated genes included Car3 that was associated with the protection of cells from attack by oxygen radicals. As for Igfbp1 (insulin like growth factor binding protein 1), we confirmed that its expression was reduced by siRNA targeting dbpA in the human HCC cell line. Less
癌症是一种体细胞的遗传性疾病。癌变看起来像一个打开的日本扇子,因为初始细胞在几个方向上生长,肿瘤表明扇子的边缘有许多基因异常。肝细胞癌(HCC)的发展与多种因素引起的肝脏慢性炎症有关,如乙型肝炎或丙型肝炎病毒感染。我们报道了DNA结合蛋白A (dbpA)作为加速炎症诱导的肝癌发生的候选分子,dbpA属于Y盒结合蛋白家族,而YB-1是该家族的原型成员,据报道是肝癌以外恶性疾病的预后标志物。本研究的目的是研究dbpA的表达,或dbpA启动子区T - G转位在体外增强启动子活性的过程中对HCC进展的意义。(1) dbpA的表达与HCC的晚期相关,且有核dbpA表达的病例预后较差。(2)DbpA对这一关联的贡献大于YB-1。(3) dbpA启动子区T - G转换与dbpA的核定位有关。我们报道了dbpA转录受到E2F1的正调控,这也与肝癌的发生有关。为了研究dbpA在体内对肝癌发生的影响,我们培育了在肝细胞中特异性表达一种转基因的dbpA转基因小鼠。我们通过微阵列分析研究了dbpA对其他细胞基因表达的影响。比较了31周龄和32周龄无形态变化的转基因雄性小鼠肝脏(Tg(+))和野生型雄鼠肝脏(Tg(-))的表达谱。(4) 11个上调基因包括7个致癌相关基因(Igfbp1、Tff3、Hpx、Orm2、Cts1、Plg、Jdp1), 9个下调基因包括与保护细胞免受氧自由基攻击相关的Car3。对于Igfbp1(胰岛素样生长因子结合蛋白1),我们证实了siRNA靶向dbpA可降低其在人HCC细胞系中的表达。少
项目成果
期刊论文数量(33)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
A mutation in the SDHC gene of complex II increases oxidative stress, resulting in apoptosis and tumorigenesis.
- DOI:10.1158/0008-5472.203.65.1
- 发表时间:2005-01
- 期刊:
- 影响因子:11.2
- 作者:Takamasa Ishii;K. Yasuda;A. Akatsuka;O. Hino;P. Hartman;N. Ishii
- 通讯作者:Takamasa Ishii;K. Yasuda;A. Akatsuka;O. Hino;P. Hartman;N. Ishii
Intentional delay of human hepatocarcinogenesis due to suppression of chronic hepatitis.
由于抑制慢性肝炎而故意延迟人类肝癌的发生。
- DOI:
- 发表时间:2005
- 期刊:
- 影响因子:0
- 作者:Ishii T.;Yasuda K.;Akatsuka A.;Hino O.;Hartman P.S.;Ishii N.;Hino O.
- 通讯作者:Hino O.
Federal headship of human hepatocarcinogenesis.
人类肝癌发生的联邦领导。
- DOI:
- 发表时间:2005
- 期刊:
- 影响因子:0
- 作者:Ishii T.;Yasuda K.;Akatsuka A.;Hino O.;Hartman P.S.;Ishii N.;Kaneko O et al.;Winter G et al.;Hino O.
- 通讯作者:Hino O.
Transgenic rescue from embryonic lethality and renal carcinogenesis in the Nihon rat model by introduction of a wild-type Bhd gene.
通过引入野生型 Bhd 基因,转基因挽救日本大鼠模型中的胚胎致死和肾癌。
- DOI:
- 发表时间:2005
- 期刊:
- 影响因子:0
- 作者:Togashi Y;Hino O.;et al.
- 通讯作者:et al.
Studies of familial tumors using models : genotype, phenotype, and dramatype in carcinogenesis.
使用模型研究家族性肿瘤:癌发生中的基因型、表型和戏剧型。
- DOI:
- 发表时间:2004
- 期刊:
- 影响因子:0
- 作者:Hino O.et al.
- 通讯作者:Hino O.et al.
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HINO Okio其他文献
HINO Okio的其他文献
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{{ truncateString('HINO Okio', 18)}}的其他基金
Rehabilitation of cancer cells
癌细胞的康复
- 批准号:
25670196 - 财政年份:2013
- 资助金额:
$ 9.54万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
Rehabilitation of cancer cells
癌细胞的康复
- 批准号:
23659206 - 财政年份:2011
- 资助金额:
$ 9.54万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
Risk evaluation of environmental carcinogenesis
环境致癌风险评估
- 批准号:
22240093 - 财政年份:2010
- 资助金额:
$ 9.54万 - 项目类别:
Grant-in-Aid for Scientific Research (A)
The study of multistep carcinogenesis using unique animal models
使用独特的动物模型研究多步致癌作用
- 批准号:
17013076 - 财政年份:2005
- 资助金额:
$ 9.54万 - 项目类别:
Grant-in-Aid for Scientific Research on Priority Areas
Multi-step carcinogenesis using genetically retired models
使用基因退休模型进行多步骤致癌
- 批准号:
12213139 - 财政年份:2000
- 资助金额:
$ 9.54万 - 项目类别:
Grant-in-Aid for Scientific Research on Priority Areas
Multistage carcinogenesis in TSC gene mutant models
TSC 基因突变模型中的多阶段致癌作用
- 批准号:
08264108 - 财政年份:1999
- 资助金额:
$ 9.54万 - 项目类别:
Grant-in-Aid for Scientific Research on Priority Areas
Pathogenesis of Human Tuberous Sclerosis
人类结节性硬化症的发病机制
- 批准号:
09470068 - 财政年份:1997
- 资助金额:
$ 9.54万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Isolation of the predisposing gene of the Eker rat model of hereditary renal cell carcinoma
Eker大鼠遗传性肾细胞癌模型易感基因的分离
- 批准号:
06454719 - 财政年份:1994
- 资助金额:
$ 9.54万 - 项目类别:
Grant-in-Aid for General Scientific Research (B)
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TRPV2在原发性肝癌中癌变作用的研究
- 批准号:81171933
- 批准年份:2011
- 资助金额:60.0 万元
- 项目类别:面上项目
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NASH-肝细胞癌免疫治疗反应的决定因素
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NF2/Merlin 在调节 Hippo/Salvador/Warts 生长控制通路中的功能
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