Analysis of HPV regulatory gene function with organotypic culture of epithelial cells.

通过上皮细胞器官型培养分析 HPV 调节基因功能。

基本信息

  • 批准号:
    13214048
  • 负责人:
  • 金额:
    $ 21.95万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research on Priority Areas
  • 财政年份:
    2001
  • 资助国家:
    日本
  • 起止时间:
    2001 至 2004
  • 项目状态:
    已结题

项目摘要

There are many cancers associated with the infection of human papillomavirus (HPV), among which cervical cancer is considered the most important one. To prevent the HPV-induced cancer development, it is essential to understand the replication cycle of HPV on the molecular basis. However, the analysis of HPV life-cycle has been hampered by a fact that the HPV replication strongly depends on the differentiation program of epithelial cells. We developed an HPV replication system with organotypic culture of keratinocyte (raft culture) and a novel HPV replicon, which enable us to analyze the HPV replication and the HPV-induced hyperplasia in vitro.With this system, we could obtain following results: (1) the efficient replication system of HPV could be adapted to the screening of anti-virus drugs, (2) activation of Ha-ras pathway conferred a malignant cell phenotype on the HPV-infected cells, (3) high-risk type E7 was responsible for the hyperplasia induction by HPV, in which the inactivation of both pRb and pl30 and the activation of JNK pathway might be involved, (4) continuous expression of E7 in the HPV-positive cervical cancer cell was essential for the cell viability and for the prevention of senescence induction, (5) E4 gene product could induce G2/M arrest in cell division cycle without preventing cellular DNA synthesis, suggesting the involvement of E4 in the viral DNA amplification in the differentiated layer of epidermis.
与人乳头瘤病毒(HPV)感染有关的癌症有很多,其中宫颈癌被认为是最重要的一种。为了预防HPV诱导的癌症发展,从分子基础上了解HPV的复制周期是至关重要的。然而,HPV的复制强烈依赖于上皮细胞的分化程序,这一事实阻碍了HPV生命周期的分析。我们开发了一种角质细胞器官型培养(筏培养)和新型HPV复制子的HPV复制系统,使我们能够在体外分析HPV复制和HPV诱导的增生。使用该系统,我们可以得到以下结果:(1) HPV的高效复制系统可以适应抗病毒药物的筛选;(2)Ha-ras通路的激活使HPV感染的细胞具有恶性细胞表型;(3)高危型E7负责HPV诱导增生,其中可能涉及pRb和pl30的失活以及JNK通路的激活。(4)在hpv阳性宫颈癌细胞中连续表达E7对细胞存活和防止衰老具有重要作用;(5)E4基因产物可诱导细胞分裂周期中G2/M阻滞,但不妨碍细胞DNA合成,提示E4参与了表皮分化层病毒DNA扩增。

项目成果

期刊论文数量(36)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Mechanisms of human papillomavirus E2-mediated repression of viral oncogene expression and cervical cancer cell growth inhibition
  • DOI:
    10.1128/jvi.74.8.3752-3760.2000
  • 发表时间:
    2000-04-01
  • 期刊:
  • 影响因子:
    5.4
  • 作者:
    Nishimura, A;Ono, T;Sakai, H
  • 通讯作者:
    Sakai, H
Analysis of dominant-negative effects of mutant Env proteins of human immunodeficiency virus type 1
  • DOI:
    10.1006/viro.2001.0944
  • 发表时间:
    2001-07-20
  • 期刊:
  • 影响因子:
    3.7
  • 作者:
    Iwatani, Y;Kawano, K;Sakai, H
  • 通讯作者:
    Sakai, H
Resistance to friend murine leukemia virus infection conferred by the Fv-4 gene is recessive but appears dominant from the effect of the immune system.
Fv-4 基因赋予的对小鼠白血病病毒感染的抵抗力是隐性的,但由于免疫系统的影响而显得显性。
  • DOI:
  • 发表时间:
    2000
  • 期刊:
  • 影响因子:
    0
  • 作者:
    張 鳳民 他
  • 通讯作者:
    張 鳳民 他
岩谷靖雅 他: "Function of hetero-oligomeric Env proteins containing mutant Env protein of human immunodeficiency virus type 1 in viral infectivity"Virology. 286. 45-53 (2001)
Yasumasa Iwatani 等:“含有人类免疫缺陷病毒 1 型突变 Env 蛋白的异源寡聚 Env 蛋白在病毒感染性中的功能”286. 45-53 (2001)。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Functional association between the nef gene product and gag‐pol region of HIV‐1
  • DOI:
    10.1016/s0014-5793(99)01791-3
  • 发表时间:
    2000-01
  • 期刊:
  • 影响因子:
    3.5
  • 作者:
    T. Ono;Y. Iwatani;A. Nishimura;A. Ishimoto;H. Sakai
  • 通讯作者:
    T. Ono;Y. Iwatani;A. Nishimura;A. Ishimoto;H. Sakai
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SAKAI Hiroyuki其他文献

SAKAI Hiroyuki的其他文献

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{{ truncateString('SAKAI Hiroyuki', 18)}}的其他基金

Understandings of the HPV-induced tumorigenesis for developing anti-virus reagents.
了解 HPV 诱导的肿瘤发生,以开发抗病毒试剂。
  • 批准号:
    23590540
  • 财政年份:
    2011
  • 资助金额:
    $ 21.95万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Development of the method of extracting causal expressions from Japanese financial articles concerning business performance and analyzing them for supporting decision on investment
开发从日本金融文章中提取有关业务绩效的因果表达式并对其进行分析以支持投资决策的方法
  • 批准号:
    21700158
  • 财政年份:
    2009
  • 资助金额:
    $ 21.95万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
ICT enabled class improvement system for university teachers
ICT 为大学教师提供课堂改进系统
  • 批准号:
    20700637
  • 财政年份:
    2008
  • 资助金额:
    $ 21.95万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
Functional analysis of HPV genes in keratinocyte organotypic culture system.
角质形成细胞器官型培养系统中HPV基因的功能分析。
  • 批准号:
    11138226
  • 财政年份:
    1999
  • 资助金额:
    $ 21.95万
  • 项目类别:
    Grant-in-Aid for Scientific Research on Priority Areas (A)
Functional interaction between gene expression and DNA replication of HPV lifecyle
HPV生命周期的基因表达和DNA复制之间的功能相互作用
  • 批准号:
    10470076
  • 财政年份:
    1998
  • 资助金额:
    $ 21.95万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Development of loricrin monoclonal antibody and its specific location
兜甲素单克隆抗体的研制及其具体定位
  • 批准号:
    06670850
  • 财政年份:
    1994
  • 资助金额:
    $ 21.95万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)

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Secondary analysis of Human Mammary Tumor Virus (HMTV) in breast cancer.
人类乳腺肿瘤病毒(HMTV)在乳腺癌中的二次分析。
  • 批准号:
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APOBEC脱氨酶在人类肿瘤病毒感染中的作用
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Pathogenesis of enzootic nasal tumor virus (ENTV)
地方性鼻肿瘤病毒(ENTV)的发病机制
  • 批准号:
    355661-2008
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    2012
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    $ 21.95万
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    Discovery Grants Program - Individual
Pathogenesis of enzootic nasal tumor virus (ENTV)
地方性鼻肿瘤病毒(ENTV)的发病机制
  • 批准号:
    355661-2008
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Pathogenesis of enzootic nasal tumor virus (ENTV)
地方性鼻肿瘤病毒(ENTV)的发病机制
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Pathogenesis of enzootic nasal tumor virus
地方性鼻肿瘤病毒的发病机制
  • 批准号:
    400816-2010
  • 财政年份:
    2010
  • 资助金额:
    $ 21.95万
  • 项目类别:
    University Undergraduate Student Research Awards
In vivo pathogenesis of enzootic nasal tumor virus reconstructed from enzootic nasal adenocarcinoma
地方性鼻腺癌重建的地方性鼻肿瘤病毒的体内发病机制
  • 批准号:
    385003-2009
  • 财政年份:
    2009
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    $ 21.95万
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    University Undergraduate Student Research Awards
Pathogenesis of enzootic nasal tumor virus (ENTV)
地方性鼻肿瘤病毒(ENTV)的发病机制
  • 批准号:
    355661-2008
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    $ 21.95万
  • 项目类别:
    Discovery Grants Program - Individual
Pathogenesis of enzootic nasal tumor virus (ENTV)
地方性鼻肿瘤病毒(ENTV)的发病机制
  • 批准号:
    355661-2008
  • 财政年份:
    2008
  • 资助金额:
    $ 21.95万
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Structure/Function of a Tumor Virus Chaperone
肿瘤病毒伴侣的结构/功能
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    6980136
  • 财政年份:
    2004
  • 资助金额:
    $ 21.95万
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