國家衛生研究院 NHRI:Item 3990099045/2663
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    題名: DNA methylation and histone modification regulate silencing of epithelial cell adhesion molecule for tumor invasion and progression
    作者: Tai, KY;Shiah, SG;Shieh, YS;Kao, YR;Chi, CY;Huang, E;Lee, HS;Chang, LC;Yang, PC;Wu, CW
    貢獻者: National Institute of Cancer Research
    摘要: Epithelial cell adhesion molecule ( Ep-CAM) is believed to have a critical role in carcinogenesis and cell proliferation. However, the association of Ep-CAM with cancer invasion and progression is less clear. We found that EpCAM was highly expressed on low-invasive cells compared with highly invasive cells. Forced expression of Ep-CAM decreased cancer invasiveness, and silencing Ep-CAM expression elevated cancer invasiveness. EpCAM expression was associated with promoter methylation. Treatment with a demethylating agent, and/or the histone deacetylase inhibitor reactivated Ep-CAM expression in Ep-CAM-negative cells and inhibited cancer invasiveness. Using a promoter-reporter construct, we demonstrated methylation of the promoter fragment drive Ep-CAM-silenced transcription. Additionally, silenced Ep-CAM gene in cancer cells was enriched for hyper-methylated histone 3 lysine 9. When unmethylated and active, this promoter was associated with acetylated histone 3 lysine 9. Furthermore, we observed an increased association of Ep-CAM promoter with repression components as tumor invasiveness increased. In cancer tissues, Ep-CAM expression significantly correlated with tumor progression and associated with promoter methylation. Our data support the idea that modulation of Ep-CAM plays a pivotal role in tumor invasion and progression. Moreover, aberrant DNA methylation of Ep-CAM is implicated in enhancing invasive/metastatic proclivity of tumors.
    關鍵詞: Biochemistry & Molecular Biology;Oncology;Cell Biology;Genetics & Heredity
    日期: 2007-06-07
    關聯: Oncogene. 2007 Jun;26(27):3989-3997.
    Link to: http://dx.doi.org/10.1038/sj.onc.1210176
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0950-9232&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000247144500009
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=34249989097
    顯示於類別:[吳成文(1996-2008)] 期刊論文
    [夏興國] 期刊論文

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