國家衛生研究院 NHRI:Item 3990099045/9949

NHRI > National Institute of Environmental Health Sciences > Hsin-Su Yu > Conference Papers/Meeting Abstract > Item 3990099045/9949

Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/9949

Title:	A synergism between arsenic-induced epigenetic modification and inflammatory promotion in a novel skin equivalent during arsenic carcinogenesis
Authors:	Liao, W;Lu, J;Lee, C;Lan, C;Chang, J;Chai, C;Yu, H
Contributors:	National Institute of Environmental Health Sciences
Abstract:	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 cellecell interactions involved in those processes remain unclear. We have established a novel human intraepidermal carcinoma skin equivalent with organotypic culture-consisting of keratinocytes (KCs), fibroblasts, and peripheral blood mononuclear cells (PBMCs)-induced by arsenic treatment. This skin equivalent demonstrates the pathognomonic characteristics of arsenic-induced Bowen’s disease (As-BD), including acanthosis, dysplasia, and dyskeratosis. Using this skin-equivalent 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-a release from PBMCs. TNF-a triggered anti-apoptotic signals via FLIPassociated caspase-8 inactivation in arsenic-treated KCs, which in turn contributed to cell survival and aneuploidy. The synergism between arsenic-induced epigenetic modification and inflammatory promotion resulted in the development of the pathognomonic features of As-BD in this novel model.
Date:	2016-09
Relation:	Journal of Investigative Dermatology. 2016 Sep;136(9, Suppl. 2):S237.
Link to:	http://dx.doi.org/10.1016/j.jid.2016.06.469
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:000383091900444
Appears in Collections:	[Hsin-Su Yu] Conference Papers/Meeting Abstract

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