Detection of Novel Drug Receptor and Mechanism of Induction of Differentiation and Apoptosis in Human Salivary Cancer Cells

人唾液癌细胞新型药物受体的检测及诱导分化和凋亡的机制

基本信息

  • 批准号:
    06404072
  • 负责人:
  • 金额:
    $ 19.46万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (A)
  • 财政年份:
    1994
  • 资助国家:
    日本
  • 起止时间:
    1994 至 1996
  • 项目状态:
    已结题

项目摘要

1.It has been found by immunofluorescent staining technique, immunoblotting, electron microscopy or immunoelectron microscopy that the treatment of human salivary cancer cell line HSG having the phenotype similar to salivary intercalated duct cells with 5-fluorodeoxyuridine monophosphate (FdUMP) results in the cellular differentiation into myoepithelial cells with the expression of myosin, beta chain of S-100 protein, pinocytic vesicles and myofilaments. In addition, it has been detected by electron microscopy, agarose gel electrophoresis or 3'-OH nick-end labelling that apoptosis is induced in the treated cells.2.It has been found by Scatchard analysis using ^3H-labelled FdUMP that HSG cells have 10^6 receptors for FdUMP/cell on cell membrane (Kd=3.7x10^<-10>M).3.We have prepared the murine monoclonal antibody (MAb) directed to the FdUMP receptors on HSG cell membranes (5B/10). It has been found that the in vitro growth inhibition of HSG cells by FdUMP is released by 5B/10 MAb. This i … More ndicates that 5B/10 MAb recognizes the epitope of FdUMP receptors. Thus, we have isolated the receptor proteins binding FdUMP (28KDa and 84KDa), by affinity chromatography using 5B/10 MAb as a ligand or by FdUMP exchange reaction. In addition, it has been found by immunofluorescent staining technique using 5B/10 MAb that the FdUMP receptors are frequently expressed in the adenocarcinoma arising in salivary gland, stomach or colon.4.We have performed the amino acid sequencing of FdUMP-binding protein. Consequently, the sequence was decoded NLDLDSIIAEVKA,which corresponded to the amino acid sequence of cytokeratin 5,6 or 8.5.We have constructed anti-sense oriented cDNA library, using mRNA isolated from HSG cells. This expression cDNA library was transfected into HSG cells and the cell clones proliferating in the presence of FdUMP were isolated. We have performed DNA sequencing for the genes recovered from the cell clones. Consequently, it has been found that proteosome gene and plectin gene encoding the adaptor protein associated with intermediate-sized filaments are related with the signal tranduction via FdUMP receptor. Less
1.免疫荧光染色、免疫印迹、电子显微镜或免疫电子显微镜观察发现,5-氟脱氧尿苷单磷酸作用于表型类似于涎腺间质管细胞的人涎腺癌细胞系HSG,可诱导细胞分化为肌上皮细胞,并表达肌球蛋白、S-100蛋白的β链、胞质小泡和肌丝。用~3H标记的FdUMP进行Scatchard分析发现,HSG细胞膜上有10^6个FdUMP受体(Kd=3.7x10^&lt;-10&gt;M)。3.我们制备了针对HSG细胞膜FdUMP受体的鼠单抗(5B/10)。结果表明,FdUMP对HSG细胞的体外生长抑制作用以5B/10MAb释放。This I…提示5B/10单抗识别FdUMP受体表位。因此,我们通过以5B/10单抗为配基的亲和层析或FdUMP交换反应,分离出与FdUMP(28 KDa和84 KDa)结合的受体蛋白。此外,用5B/10单抗免疫荧光染色技术发现,FdUMP受体在涎腺、胃或结肠腺癌中表达频率较高。4.对FdUMP结合蛋白进行了氨基酸序列测定。在此基础上,对该序列进行了NLDLDSIIAEVKA解码,该序列与细胞角蛋白5、6或8.5的氨基酸序列相对应。将该表达文库导入HSG细胞,分离出在FdUMP作用下增殖的细胞克隆。我们已经对从细胞克隆中恢复的基因进行了DNA测序。结果发现,编码与中等细丝相关的适配蛋白的蛋白体基因和plectin基因与FdUMP受体的信号转导有关。较少

项目成果

期刊论文数量(67)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Masayuki Azuma: "Proteolytic enzymes in salivary extravasation mucoceles" J.Oral.Pathol.Med.24. 299-302 (1995)
Masayuki Azuma:“唾液外渗粘液囊肿中的蛋白水解酶”J.Oral.Pathol.Med.24。
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    0
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Hitoshi Kawamata: "Possible contribution of active MMP2 to lymph-node metastasis and secreted cathepsin L to bone invasion of newly established human oral cancer cell lines." Int.J.Cancer. 70. 120-127 (1997)
Hitoshi Kawamata:“活性 MMP2 可能有助于淋巴结转移,分泌的组织蛋白酶 L 可能有助于新建立的人类口腔癌细胞系的骨侵袭。”
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    0
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Masayuki Azuma: "Increased matrix metalloproteinase-2 activity induced by TGF-β1 induct cells of human salivary gland is associated with the development of cyst formation in vivo" J Oral Pathol Med.25. 467-473 (1996)
Masayuki Azuma:“人唾液腺 TGF-β1 诱导细胞诱导的基质金属蛋白酶 2 活性增加与体内囊肿形成的发展有关”J Oral Pathol Med.25 (1996)。
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    0
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  • 通讯作者:
Takada H,Kawabata Y,Arakaki R,Kusumoto S,Fukase K,Suda Y,Yoshimura T,Kokeguchi S,Kato K,Komuro T,Tanaka N,Saito M,Yoshida T,Sato M and Kotani S.: "Molecular and structural requirements of a lipoteichoic acid from enterococcus hirae for cytokine-inducing,
Takada H,Kawabata Y,Arakaki R,Kusumoto S,Fukase K,Suda Y,Yoshimura T,Kokeguchi S,Kato K,Komoro T,Tanaka N,Saito M,Yoshida T,Sato M和Kotani S.:“分子和结构
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    0
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Harada K,Yura Y,Tsujimoto H,Kusaka J,Yoshida H and Sato M.: "Effect of local administration of epidermal growth factor on 9,10-dimethyl-1,2-benzanthracene-induced tumour formation in hamster cheek pouch." Oral Oncol Eur J Cancer. 31B(1). 27-31 (1995)
Harada K、Yura Y、Tsujimoto H、Kusaka J、Yoshida H 和 Sato M.:“局部施用表皮生长因子对 9,10-二甲基-1,2-苯并蒽诱导的仓鼠颊囊肿瘤形成的影响”。
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    0
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SATO Mitsunobu其他文献

SATO Mitsunobu的其他文献

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

Syntheses of apatite via Ca complexes of amino acids involved innon-collagen protein
通过参与非胶原蛋白的氨基酸的 Ca 络合物合成磷灰石
  • 批准号:
    22550183
  • 财政年份:
    2010
  • 资助金额:
    $ 19.46万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Toll-like receptor 4 signaling : Enhancement of therapeutic effect of anti-cancer drugs and radiation in oral Cancer
Toll样受体4信号传导:增强口腔癌的抗癌药物和放射治疗效果
  • 批准号:
    14207090
  • 财政年份:
    2002
  • 资助金额:
    $ 19.46万
  • 项目类别:
    Grant-in-Aid for Scientific Research (A)
Development of the therapy for oral cancer by transduction of iNOS gene in combination with radiotherapy
iNOS基因转导联合放疗治疗口腔癌的进展
  • 批准号:
    12557176
  • 财政年份:
    2000
  • 资助金额:
    $ 19.46万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Study on differentiation and apoptosis-inducing therapy for head and neck cancer by vesnarinone
维纳里酮诱导头颈癌分化和凋亡的研究
  • 批准号:
    10307051
  • 财政年份:
    1998
  • 资助金额:
    $ 19.46万
  • 项目类别:
    Grant-in-Aid for Scientific Research (A)
Lipoteichoic acid : Augmentation of the therapeutic effect of radiation and 5-fluorouracil in head and neck cancer
脂磷壁酸:增强放射线和5-氟尿嘧啶对头颈癌的治疗效果
  • 批准号:
    09557170
  • 财政年份:
    1997
  • 资助金额:
    $ 19.46万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Development of screening system for searching cellular differentiation-inducing agents by utlizing human salivary cancer cells
开发利用人唾液癌细胞寻找细胞分化诱导剂的筛选系统
  • 批准号:
    05557084
  • 财政年份:
    1993
  • 资助金额:
    $ 19.46万
  • 项目类别:
    Grant-in-Aid for Developmental Scientific Research (B)
Study of Differentiation Therapy for Salivary Gland Cancer
唾液腺癌的分化治疗研究
  • 批准号:
    03454467
  • 财政年份:
    1991
  • 资助金额:
    $ 19.46万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (B)
Development of Multi-functional Ligands for Application of Metal Complexes
金属配合物应用多功能配体的开发
  • 批准号:
    03650687
  • 财政年份:
    1991
  • 资助金额:
    $ 19.46万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)
Local Immunotherapy of Oral Cancer with LAK Cells and Interleukin 2
LAK 细胞和白细胞介素 2 治疗口腔癌的局部免疫疗法
  • 批准号:
    63870080
  • 财政年份:
    1988
  • 资助金额:
    $ 19.46万
  • 项目类别:
    Grant-in-Aid for Developmental Scientific Research

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The Conundrum of Absentee Receptors: Efficacy Potentiation Through Drug-Receptor Modulation
缺失受体的难题:通过药物受体调节增强功效
  • 批准号:
    10708018
  • 财政年份:
    2022
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Integrated approaches to targeting G protein-coupled receptors: Translational studies of novel drug-receptor paradigms
靶向 G 蛋白偶联受体的综合方法:新型药物受体范例的转化研究
  • 批准号:
    nhmrc : 1102950
  • 财政年份:
    2016
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    Research Fellowships
Integrated approaches to targeting G protein-coupled receptors: Translational studies of novel drug-receptor paradigms
靶向 G 蛋白偶联受体的综合方法:新型药物受体范例的转化研究
  • 批准号:
    nhmrc : GNT1102950
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    2016
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THEORETICAL AND COMPUTATIONAL ANALYSES OF DRUG-RECEPTOR INTERACTION CONSIDERING HYDROPHOBIC INTERACTION
考虑疏水相互作用的药物-受体相互作用的理论和计算分析
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    20590036
  • 财政年份:
    2008
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Probing drug receptor binding sites driven by solid state NMR - An interdisciplinary approach.
由固态 NMR 驱动的药物受体结合位点探测 - 一种跨学科方法。
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    EP/E000177/1
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    2006
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Probing drug receptor binding sites driven by solid state NMR - An interdisciplinary approach.
由固态 NMR 驱动的药物受体结合位点探测 - 一种跨学科方法。
  • 批准号:
    EP/E000290/1
  • 财政年份:
    2006
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Analysis of urinary dysfunction and drug discovery by in vivo measurement of drug-receptor binding
通过体内药物受体结合测量分析泌尿功能障碍和药物发现
  • 批准号:
    18590237
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    2006
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PREDICTION OF STRUCTURES AND BINDING CONSTANTS OF DRUG-RECEPTOR COMPLEXES BY HYDROPHOBIC SURFACE AREAS
通过疏水表面区域预测药物受体复合物的结构和结合常数
  • 批准号:
    11672153
  • 财政年份:
    1999
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Drug receptor function and its regulation
药物受体功能及其调控
  • 批准号:
    05304026
  • 财政年份:
    1993
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    $ 19.46万
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    Grant-in-Aid for Co-operative Research (A)
Development of computer system for generating drug structures based on drug-receptor interaction
基于药物-受体相互作用生成药物结构的计算机系统的开发
  • 批准号:
    01870094
  • 财政年份:
    1989
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