國家衛生研究院 NHRI:Item 3990099045/2666
English  |  正體中文  |  简体中文  |  全文筆數/總筆數 : 12145/12927 (94%)
造訪人次 : 925398      線上人數 : 781
RC Version 6.0 © Powered By DSPACE, MIT. Enhanced by NTU Library IR team.
搜尋範圍 查詢小技巧：
  • 您可在西文檢索詞彙前後加上"雙引號"，以獲取較精準的檢索結果
  • 若欲以作者姓名搜尋，建議至進階搜尋限定作者欄位，可獲得較完整資料
    •  進階搜尋
    主頁 ‧ 登入 ‧ 上傳 ‧ 說明 ‧ 關於NHRI ‧ 管理 到手機版


    請使用永久網址來引用或連結此文件: http://ir.nhri.org.tw/handle/3990099045/2666


    題名: Up-regulation of vascular endothelial growth factor C in breast cancer cells by heregulin-beta 1
    作者: Tsai, PW;Shiah, SG;Lin, MT;Wu, CW;Kuo, ML
    貢獻者: National Institute of Cancer Research
    摘要: Vascular endothelial growth factor C (VEGF-C) is a critical activator of tumor lymphangiogenesis that recently has been strongly implicated in the tumor metastasis process. In this study, we identified that HRG-beta1 stimulated up-regulation of VEGF-C mRNA and protein of human breast cancer cells in a dosage- and time-dependent manner and that this up-regulation was de novo RNA synthesis-dependent. The HRG-beta1-induced increase in VEGF-C expression was effectively reduced by treatment with Herceptin, an antibody specifically against HER2. Also, when HER2 was overexpressed in MCF-7 cells that resulted in an evident increase in the VEGF-C level, suggesting an essential role of HER2 in mediating VEGF-C up-regulation by HRG-beta1. NF-kappaB has been shown to be probably involved in interleukin-1beta-or tumor necrosis factor-alpha-induced VEGF-C mRNA expression in human fibroblasts. Here we found that HRG-beta1 could stimulate NF-kappaB nuclear translocation and DNA-binding activity via the IkappaBalpha phosphorylation-degradation mechanism. Blockage of the NF-kappaB activation cascade caused a complete inhibition of the HRG-beta1-induced elevation of VEGF-C. In promoter-reporter assay, the luciferase activities of the reporter constructs, including the putative NF-kappaB site deleted and mutated form were significantly reduced after HRG-beta1 treatment as compared with the 1.5-kb VEGF-C promoter. Although investigating the upstream kinase pathway(s) involved in HRG-beta1-elicited NF-kappaB activation and VEGF-C up-regulation, we found that HRG-beta1 could activate extracellular signal-regulated protein kinase 1/2, phosphatidylinositol 3'-kinase, and p38 mitogen-activated protein kinase (MAPK) in MCF-7. However, only SB203580 (a specific inhibitor of p38 MAPK), not PD98059 nor LY294002, blocked the up-regulation of VEGF-C by HRG-beta1. A similar inhibition in VEGF-C expression was obtained by cell transfection with dominant-negative p38 (p38AF). Interestingly, the HRG-beta1-induced NF-kappaB activation cascade was also effectively blocked by SB203580 treatment or p38AF transfection. Our data thus suggests that HRG-beta1 stimulated a NF-kappaB-dependent up-regulation of VEGF-C through the p38 MAPK signaling pathway in human breast cancer cells.
    關鍵詞: Biochemistry & Molecular Biology
    日期: 2003-02-21
    關聯: Journal of Biological Chemistry. 2003 Feb;278(8):5750-5759.
    Link to: http://dx.doi.org/10.1074/jbc.M204863200
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1083-351X&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000181129400035
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=0037458645
    顯示於類別:[吳成文(1996-2008)] 期刊論文
    [夏興國] 期刊論文

    文件中的檔案:

    檔案 描述 大小格式瀏覽次數
    000181129400035.pdf563KbAdobe PDF762檢視/開啟


    在NHRI中所有的資料項目都受到原著作權保護.

    TAIR相關文章

    DSpace Software Copyright © 2002-2004  MIT &  Hewlett-Packard  /   Enhanced by   NTU Library IR team Copyright ©   - 回饋