Basic research of annexin V as a molecular target therapy for gynecologic cancer

膜联蛋白V作为妇科肿瘤分子靶向治疗的基础研究

基本信息

  • 批准号:
    14571536
  • 负责人:
  • 金额:
    $ 2.24万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
  • 财政年份:
    2002
  • 资助国家:
    日本
  • 起止时间:
    2002 至 2003
  • 项目状态:
    已结题

项目摘要

Recently, molecular mechanism of proliferation and progression of carcinoma cells (infiltration and invasion) has been well understood. As a result, molecular target therapy of cancer patient is developing in Europe and the United States. Clinical trials of some tyrosine kinase inhibitors have already carried out as anti -cancer drugs. Although protein kinase C (PKC) representing Ser/Thr protein kinases is one of the most important kinases, no endogenous inhibitor in the cell has not been discovered. We first separated and purified annexin V from human placenta, which was a Ca^<2+>-dependent phospholipid binding protein, and reported to inhibite protein kinase C activity in vitro. The purpose of this study is to elucidate the role of annexin V in the cell and to clarify whether annexin V can inhibit tumor progression in the cell, followed by developing molecular target therapy of cancer patients with Ser/Thr protein kinase inhibitors by inhibiting tumor progression.We constructed annex … More in V-stably expressing human leukemia cell lines (HL-60). Although annexin V overexpression did not induce morphological changes in the cell lines, TPA-induced PKC activation was inhibited in annexin V overexpressing cells. We showed that PKCδ was a most likely, candidate of TPA targeting PKC isoforms that was inhibited by annexin V. Since annexin V overexpress ion did not induce phenotype, we approached biological function of annexin V by the elucidation of annexin V gene regulation. Our results suggest that (i)protein synthesis inhibitors (CHX, ANI) superinduce annexin V mRNA expression. (ii)TPA enhances CHX-induced the superinduction of annexin V mRNA in MCAS cells by activating PKC and mRNA transcription. (iii)ANI superinduces annexin V mRNA expression through the ERK1/2 MAPK pathway, but not through the p38 MAPK pathway. Taken together, these results indicated that the regulation of annexin V gene expression was negatively controlled at the transcription factor level, and that PKC and ERK1/2 pathway was involved in the induction of annexin V gene expression. Less
近年来,肿瘤细胞增殖和发展的分子机制(浸润性和侵袭性)已被人们所熟知。因此,肿瘤患者的分子靶向治疗正在欧美国家蓬勃发展。一些酪氨酸激酶抑制剂已经作为抗癌药物进行了临床试验。代表丝氨酸/苏氨酸蛋白激酶的蛋白激酶C(PKC)是最重要的蛋白激酶之一,但尚未发现细胞内的内源性抑制物。我们首次从人胎盘中分离和纯化了膜联蛋白V,它是一种依赖于钙离子的磷脂结合蛋白,据报道在体外可以抑制蛋白激酶C的活性。本研究的目的是阐明Annexin V在细胞中的作用,并阐明Annexin V是否能抑制细胞内的肿瘤进展,进而开发应用丝氨酸/苏氨酸蛋白激酶抑制剂抑制肿瘤进展的分子靶向治疗癌症患者。我们构建了附件…在V-稳定表达的人白血病细胞系(HL-60)中更多。虽然Annexin V过表达不会引起细胞形态的改变,但在Annexin V过表达的细胞中,TPA诱导的PKC活化被抑制。我们发现PKCδ是最有可能的针对膜联蛋白V抑制的蛋白激酶C亚型的候选蛋白,由于膜联蛋白V的过度表达不能诱导表型,因此我们通过阐明膜联蛋白V基因的调控来探讨膜联蛋白V的生物学功能。我们的结果提示:(1)蛋白质合成抑制剂(CHX、ANI)可明显诱导Annexin V基因的表达。(2)TPA通过激活PKC和mRNA转录,增强CHX诱导的MCAS细胞Annexin V mRNA的超诱导。(3)ANI通过ERK1/2 MAPK途径,而不是通过p38 MAPK途径,上调Annexin V mRNA的表达。综上所述,这些结果表明Annexin V基因表达的调控在转录因子水平上是负调控的,PKC和ERK1/2通路参与了Annexin V基因表达的诱导。较少

项目成果

期刊论文数量(18)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Yoshitomo Konishi: "12-O-tetradecanoylphorbol-13-acetate enhances superinduction of annexin V mRNA express on by cycloheximide in MCAS cells"Biochem Biophys Res Commun.. (in press). (2004)
Yoshitomo Konishi:“12-O-十四烷酰佛波醇-13-乙酸酯增强放线菌酮在 MCAS 细胞中对膜联蛋白 V mRNA 表达的超诱导”Biochem Biophys Res Commun..(出版中)。
  • DOI:
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  • 影响因子:
    0
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  • 通讯作者:
Yoshitomo Konishi: "Anisomycin superinduces annexin V mRNA expression through the ERK1/2 but not th p38 MAP kinase pathway"Biochem Biophys Res Commun.. 313. 977-983 (2004)
Yoshitomo Konishi:“茴香霉素通过 ERK1/2 但不是 p38 MAP 激酶途径超级诱导膜联蛋白 V mRNA 表达”Biochem Biophys Res Commun.. 313. 977-983 (2004)
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  • 影响因子:
    0
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Hirokazu Sato: "12-O-tetradecanoylphorbol-13-acetate induces annexin V expression through the extracellular signal-regulated kinase (ERK) signaling pathway in HL-60 cells"Oncogene. (in press). (2004)
Hirokazu Sato:“12-O-tetradecanoylphorbol-13-acetate 通过细胞外信号调节激酶 (ERK) 信号通路在 HL-60 细胞中诱导膜联蛋白 V 表达”Oncogene。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Yoshitomo Konishi: "Anisomycin superinduces annexin V mRNA expression through the ERK1/2 but not the p38 MAP kinase pathway."Biochem Biophys Res Commun.. 313. 977-983 (2004)
Yoshitomo Konishi:“茴香霉素通过 ERK1/2 但不是 p38 MAP 激酶途径超级诱导膜联蛋白 V mRNA 表达。”Biochem Biophys Res Commun.. 313. 977-983 (2004)
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Yoshitomo Konishi: "12-O-tetradecanoylphorbol-13-acetate enhances superinduction of annexin V mRNA expression by cycloheximide in MCAS cells"Biochem Biophys Res Commun.. (in press). (2004)
Yoshitomo Konishi:“12-O-十四烷酰佛波醇-13-乙酸酯通过放线菌酮在 MCAS 细胞中增强膜联蛋白 V mRNA 表达的超诱导”Biochem Biophys Res Commun..(出版中)。
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    0
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SATO Hirokazu其他文献

SATO Hirokazu的其他文献

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{{ truncateString('SATO Hirokazu', 18)}}的其他基金

Contrastive research of accent and tone languages based on dynamics of suprasegmentals
基于超音段动力学的重音语言对比研究
  • 批准号:
    26284057
  • 财政年份:
    2014
  • 资助金额:
    $ 2.24万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Promotion of Early Inundated Water Drainage Using Artificial Levee Break
利用人工决堤促进早期淹没排水
  • 批准号:
    24710207
  • 财政年份:
    2012
  • 资助金额:
    $ 2.24万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
Comparative study on suprasegmental characteristics among East and Southeast Asian languages
东亚和东南亚语言超音段特征比较研究
  • 批准号:
    23300093
  • 财政年份:
    2011
  • 资助金额:
    $ 2.24万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Application of annexin V to measurement of platelete activation
膜联蛋白V在血小板活化测定中的应用
  • 批准号:
    18591793
  • 财政年份:
    2006
  • 资助金额:
    $ 2.24万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
An analysis of the system of "Bibliotheque de Travil" in Pedagogie Freinet
弗雷内教育学中“旅行图书馆”体系分析
  • 批准号:
    02610115
  • 财政年份:
    1990
  • 资助金额:
    $ 2.24万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)

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阿尔茨海默病中的异常蛋白激酶 C 信号转导
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    2023
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蛋白激酶C与肺癌发生
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    10733467
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蛋白激酶 C 介导的肿瘤进展的效应器
  • 批准号:
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Regulation of placental epithelial cell death by atypical protein kinase-c
非典型蛋白激酶-c对胎盘上皮细胞死亡的调节
  • 批准号:
    573074-2022
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非典型蛋白激酶-C 亚型对滋养层干细胞稳态和分化的调节
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    RGPIN-2021-02807
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    Discovery Grants Program - Individual
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非典型蛋白激酶-C 亚型对滋养层干细胞稳态和分化的调节
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