Proteomic analysis of molecular-targeted therapy against KGFR of salivary gland carcinomas

唾液腺癌 KGFR 分子靶向治疗的蛋白质组学分析

基本信息

  • 批准号:
    18592184
  • 负责人:
  • 金额:
    $ 2.52万
  • 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:
    2006
  • 资助国家:
    日本
  • 起止时间:
    2006 至 2007
  • 项目状态:
    已结题

项目摘要

KGF, one of fibroblast growth factor receptor, is a receptor gene of KGF/FGF-7. We clarified salivary gland tumors accompany the abnormal expression or over-expression of FGF-2 in the process of malignant alteration, furthermore, KGFR gene expression disappeared and FGFR1-IIIc gene, receptor gene of FGF-2 without expression in salivary gland epithelium usually, increase as the enlarging malignancy.In this study, gene expressions were analyzed systematically and exhaustively for salivary gland carcinoma cells transfected wild-type KGFR, gene and control carcinoma cells. And we analyzed not only construction or change in function of oncogene and tumor suppressor gene products but also expression level of interfaced proteins and modified change after translation. FGF2-FGFR1-IIIc system was blocked through inhibition of FGFR1-IIIc expression using shRNA expression vector. The proliferation potency of cells transferred FGFR1-IIIc siRNA decreased. The gene and protein groups by related cell differentiation and apoptosis inducted with manipulation of FGF-FGFR signal were analyzes by DNA micro array and proteome system.In the results, about 900 gene expressions of salivary gland carcinoma transferred wild type KGFR gene were increased. Although about 400 gene expressions were decreased. Variation of gene expressions related apoptosis, carcinogenesis, cell cycle and molecular transducer were recognized. Compared gene expression of cells transfected KGFR gene with cells transfferd FGFR1 siRNA, above 50 genes were overlapped Next proteomic analysis of protein group interlocking FGFR was performed. Above 80 protein spots varied twice were detected. In contrast, above 100 protein spots were changed by transfection of FGFR1 siRNA.
KGF是成纤维细胞生长因子受体的一种,是KGF/FGF-7的受体基因。我们明确了涎腺肿瘤在恶变过程中伴随着成纤维细胞生长因子-2的异常表达或过度表达,而且KGFR基因的表达消失,而在涎腺上皮细胞中不表达的FGFR1-IIIc基因通常会随着肿瘤的扩大而增加。我们不仅分析了癌基因和抑癌基因产物的结构或功能的变化,而且还分析了结合蛋白的表达水平和翻译后的修饰变化。利用shRNA表达载体抑制FGFR1-IIIc的表达,从而阻断FGF2-FGFR1-IIIc系统。转导FGFR1-IIIc siRNA的细胞增殖能力下降。利用DNA微阵列和蛋白质组系统分析了野生型KGFR基因在涎腺癌细胞中的表达,发现野生型KGFR基因在涎腺癌细胞中的表达增加了约900个。虽然约有400个基因表达下调。发现与细胞凋亡、肿瘤发生、细胞周期和分子转导相关的基因表达的变化。比较转导KGFR基因的细胞和转导FGFR1siRNA的细胞的基因表达,将以上50个基因重叠后进行蛋白质组互锁FGFR分析。共检测到80多个两次变异的蛋白质点。而FGFR1siRNA可使100多个蛋白质斑点发生改变。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Immunohistochemical expression of heparin-binding protein 17/fibroblast growth factor-binding protein-1 (HBp17/FGFRBP-1) as an angiogenic factor in head and neck tumorigenesis.
肝素结合蛋白 17/成纤维细胞生长因子结合蛋白-1 (HBp17/FGFRBP-1) 作为头颈部肿瘤发生中的血管生成因子的免疫组织化学表达。
  • DOI:
  • 发表时间:
    2007
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Begum S;Zhang Y;Shintani T;Toratani S;Sato JD;Okamoto T.:
  • 通讯作者:
    Okamoto T.:
Reply to letter to Editor
回复给编辑的信
  • DOI:
    10.1016/j.ijcard.2020.03.015
  • 发表时间:
    2020
  • 期刊:
  • 影响因子:
    3.5
  • 作者:
    Yamamoto Keiko;Nishimura Rintaro;Kato Fumiaki;Naito Akira;Suda Rika;Sekine Ayumi;Jujo Takayuki;Shigeta Ayako;Sakao Seiichiro;Tanabe Nobuhiro;Tatsumi Koichiro
  • 通讯作者:
    Tatsumi Koichiro
Immunohistochemical expression of heparin-binding protein17/fib roblast growth factor-binding protein-1(HBp17/FGFRBP-1) as an angiogenic factor in head and neck tumorigenesis.
肝素结合蛋白 17/纤维母细胞生长因子结合蛋白 1(HBp17/FGFRBP-1)作为头颈部肿瘤发生中的血管生成因子的免疫组织化学表达。
  • DOI:
  • 发表时间:
    2007
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Begum S;Zhang Y;Shintani T;Toratani S;Sato J D;Okamoto T.
  • 通讯作者:
    Okamoto T.
Immunohistochemical expression of heparin-binding protein 17/fibroblast growth factor-binding protein (HBpl7/FGFBP-1)as an angiogenic factor in head and neck tumorigenesis
肝素结合蛋白17/成纤维细胞生长因子结合蛋白(HBpl7/FGFBP-1)作为头颈部肿瘤发生中血管生成因子的免疫组织化学表达
  • DOI:
  • 发表时间:
    2007
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Begum;S.;Zhang;Y.;Shintani;T.;Toratani;S.;Sato;JD.;Tetsuji Okamoto
  • 通讯作者:
    Tetsuji Okamoto
Immunohistochemical expression of heparin-binding protein 17/fibroblast growth factor-binding protein (HBp17/FGFBP-1) as an angiogenic factor in head and neck tumorigenesis.
肝素结合蛋白 17/成纤维细胞生长因子结合蛋白 (HBp17/FGFBP-1) 作为头颈部肿瘤发生中的血管生成因子的免疫组织化学表达。
  • DOI:
  • 发表时间:
    2007
  • 期刊:
  • 影响因子:
    0
  • 作者:
    S.Begum;Y.Zhang;et al.
  • 通讯作者:
    et al.
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TORATANI Shigeaki其他文献

TORATANI Shigeaki的其他文献

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{{ truncateString('TORATANI Shigeaki', 18)}}的其他基金

Development of targeting therapy using specific difference of lipid composition of oral cancer cell, resistant
利用口腔癌细胞脂质成分的特异性差异开发靶向治疗,耐药
  • 批准号:
    13672098
  • 财政年份:
    2001
  • 资助金额:
    $ 2.52万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Development of photodynamic therapy to early stage oral cancer using drug delivery system
使用药物输送系统开发早期口腔癌光动力疗法
  • 批准号:
    11470438
  • 财政年份:
    1999
  • 资助金额:
    $ 2.52万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B).
New targeting therapy with complex of liposome, consist of comparable lipid composition of oral cancer cells, and anti-EGF receptor antibody.
采用脂质体复合物的新型靶向治疗,由口腔癌细胞的相似脂质成分和抗 EGF 受体抗体组成。
  • 批准号:
    10557191
  • 财政年份:
    1998
  • 资助金额:
    $ 2.52万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Development of new drug deliverty system with liposome consist of comparable to the lipid composition of oral cancer cancer cell membrane
开发新的脂质体药物递送系统,其组成与口腔癌癌细胞膜的脂质成分相当
  • 批准号:
    08672311
  • 财政年份:
    1996
  • 资助金额:
    $ 2.52万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
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