國家衛生研究院 NHRI:Item 3990099045/2142
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    题名: Epigenetic activation of alpha 4, beta 2 and beta 6 integrins involved in cell migration in trichostatin A-treated Hep3B cells
    作者: Lin, KT;Yeh, SH;Chen, DS;Chen, PJ;Jou, YS
    贡献者: Division of Molecular and Genomic Medicine
    摘要: The epigenetic modulation by histone deacetylase (HDAC) inhibitors including trichostatin A (TSA) has been known to block cell proliferation, induce apoptosis and inhibit cell migration in human cancer cells that represents the potential therapeutic agents for cancers and fibrosis. However, more than 55% of Hep3B cells remained alive after our initial study of 100 nM TSA treatment. To further study the epigenetic modulation and the biological function of newly activated genes by HDAC inhibitor involved in HCC progression and metastasis, we profiled 23 integrin genes including 15 alpha and 8 beta in TSA-treated Hep3B cells. Six integrins including three down-regulated alpha 6, alpha 10, beta 8 and three significant up-regulated alpha 4, beta 2, beta 6 integrins were revealed after semi-quantitative RT-PCR. To confirm the epigenetic modulation and explore their biological functions, we selected the three significantly up-regulated integrins for confirmation of protein up-regulation, hyperacetylated-histones by ChIP assays, and functional inhibition by specific neutralizing antibodies of integrins. Our results indicated that epigenetic modulation in TSA-treated Hep3B cells up-regulated new integrins including alpha 4, beta 2 and beta 6 and reduced migration activities by specific neutralizing antibodies to 61.3%, 42.4% and 34.5%, respectively. Our novel findings provided a better understanding of the epigenetic modulation of integrins and suggested that targeting the epigenetic up-regulated integrins to abrogate the migration activity might be a promising strategy to prevent HCC progression.
    关键词: Medicine, Research & Experimental
    日期: 2005-10
    關聯: Journal of Biomedical Science. 2005 Oct;12(5):803-813.
    Link to: http://dx.doi.org/10.1007/s11373-005-9005-2
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1021-7770&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000233238400009
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=27744473741
    显示于类别:[周玉山(1996-2005)] 期刊論文
    [葉秀慧(2001-2005)] 期刊論文

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