國家衛生研究院 NHRI:Item 3990099045/7792
English  |  正體中文  |  简体中文  |  全文筆數/總筆數 : 12145/12927 (94%)
造訪人次 : 911873      線上人數 : 1024
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/3990099045/7792


    題名: Downregulation of a putative tumor suppressor BMP4 by SOX2 promotes growth of lung squamous cell carcinoma
    作者: Fang, WT;Fan, CC;Li, SM;Jang, TH;Lin, HP;Shih, NY;Chen, CH;Wang, TY;Huang, SF;Lee, AY;Liu, YL;Tsai, FY;Huang, CT;Yang, SJ;Yen, LJ;Chuu, CP;Chen, CY;Hsiung, CA;Chang, JY;Wang, LH;Chang, IS;Jiang, SS
    貢獻者: National Institute of Cancer Research;Division of Biostatistics and Bioinformatics;Institute of Molecular and Genomic Medicine;Institute of Cellular and Systems Medicine
    摘要: SOX2 is a transcription factor essential for self-renewal and pluripotency of embryonic stem cells. Recently, SOX2 was found overexpressed in the majority of the lung squamous cell carcinoma (SQC), in which it acts as a lineage-survival oncogene. However, downstream targets/pathways of SOX2 in lung SQC cells remain to be identified. Here, we show that BMP4 is a downstream target of SOX2 in lung SQC. We found that SOX2-silencing-mediated inhibition of cell growth was accompanied by upregulation of BMP4 mRNA and its protein expression. Meta-analysis with 293 samples and qRT-PCR validation with 73 clinical samples revealed an inversely correlated relationship between levels of SOX2 and BMP4 mRNA, and significantly lower mRNA levels in tumor than in adjacent normal tissues. This was corroborated by immunohistochemistry analysis of 35 lung SQC samples showing lower BMP4 protein expression in tumor tissues. Cell-based experiments including siRNA transfection, growth assay and flow cytometry assay, further combined with a xenograft tumor model in mice, revealed that reactivation of BMP4 signaling could partially account for growth inhibition and cell cycle arrest in lung SQC cells upon silencing SOX2. Finally, chromatin immunoprecipitation analysis and luciferase reporter assay revealed that SOX2 could negatively regulate BMP4 promoter activity, possibly through binding to the promoter located in the first intron region of BMP4. Collectively, our findings suggest that BMP4 could act as a tumor suppressor and its downregulation by elevated SOX2 resulting in enhanced growth of lung SQC cells.
    日期: 2014-08
    關聯: International Journal of Cancer. 2014 Aug;135(4):809–819.
    Link to: http://dx.doi.org/10.1002/ijc.28734
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0020-7136&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000337607600005
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84902285847
    顯示於類別:[江士昇] 期刊論文
    [張憶壽] 期刊論文
    [張俊彥] 期刊論文
    [李岳倫] 期刊論文
    [施能耀] 期刊論文
    [熊昭] 期刊論文
    [王陸海] 期刊論文
    [黃秀芬] 期刊論文
    [褚志斌] 期刊論文
    [顏伶汝] 期刊論文

    文件中的檔案:

    檔案 描述 大小格式瀏覽次數
    PUB24477565.pdf761KbAdobe PDF731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