國家衛生研究院 NHRI:Item 3990099045/9997
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    题名: An Interaction between arsenic-induced epigenetic modification and inflammatory promotion in a skin equivalent during arsenic carcinogenesis
    作者: Liao, WT;Lu, JH;Lee, CH;Lan, CE;Chang, JG;Chai, CY;Yu, HS
    贡献者: National Institute of Environmental Health Sciences
    摘要: Animal studies have shown that chemical carcinogenesis consists of a 3-stage process: initiation, promotion, and progression. However, due to the lack of a suitable tissue model, the molecular mechanisms of cell-cell interactions involved in those processes remain unclear. We have established a human intraepidermal carcinoma skin equivalent (SE) with organotypic culture - consisting of keratinocytes (KCs), fibroblasts, and peripheral blood mononuclear cells (PBMCs) - induced by arsenic treatment. This SE demonstrates the pathognomonic characteristics of arsenic-induced Bowen's disease (As-BD), including acanthosis, dysplasia, and dyskeratosis. Using this SE model, we demonstrated that arsenic initiated SUV39H2-mediated epigenetic modification of E2F1, which induced centrosome amplification in KCs in 2 days; this, however, led to caspase-8 mediated apoptosis in 10 days. In parallel, arsenic stimulated TNF-alpha release mainly from PBMCs. TNF-alpha triggered anti-apoptotic signals via FLIP-associated caspase-8 inactivation in arsenic-treated KCs, which in turn contributed to cell survival and aneuploidy. The interaction between arsenic-induced epigenetic modification and inflammatory promotion resulted in the development of the pathognomonic features of As-BD in this model.
    日期: 2017-01
    關聯: Journal of Investigative Dermatology. 2017 Jan;137(1):187-196.
    Link to: http://dx.doi.org/10.1016/j.jid.2016.08.017
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0022-202X&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000390316300028
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85006819434
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