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Role of the Slug Transcription Factor in Chemically-Induced Skin Cancer

Department of Epigenetics and Molecular Carcinogenesis, University of Texas M.D. Anderson Cancer Center, P.O. Box 389, Smithville, TX 78957, USA
Program in Toxicology and Pharmacology, College of Pharmacy, University of New Mexico Health Sciences Center, MSC 09 5360, 1 University of New Mexico, Albuquerque, NM 87131, USA
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editors: David A. Brenner, Tatiana Kisseleva and Jonas Fuxe
J. Clin. Med. 2016, 5(2), 21;
Received: 12 November 2015 / Revised: 15 January 2016 / Accepted: 25 January 2016 / Published: 3 February 2016
(This article belongs to the Special Issue Epithelial-Mesenchymal Transition)
PDF [1684 KB, uploaded 3 February 2016]


The Slug transcription factor plays an important role in ultraviolet radiation (UVR)-induced skin carcinogenesis, particularly in the epithelial-mesenchymal transition (EMT) occurring during tumor progression. In the present studies, we investigated the role of Slug in two-stage chemical skin carcinogenesis. Slug and the related transcription factor Snail were expressed at high levels in skin tumors induced by 7,12-dimethylbenz[α]anthracene application followed by 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment. TPA-induced transient elevation of Slug and Snail proteins in normal mouse epidermis and studies in Slug transgenic mice indicated that Slug modulates TPA-induced epidermal hyperplasia and cutaneous inflammation. Although Snail family factors have been linked to inflammation via interactions with the cyclooxygenase-2 (COX-2) pathway, a pathway that also plays an important role in skin carcinogenesis, transient TPA induction of Slug and Snail appeared unrelated to COX-2 expression. In cultured human keratinocytes, TPA induced Snail mRNA expression while suppressing Slug expression, and this differential regulation was due specifically to activation of the TPA receptor. These studies show that Slug and Snail exhibit similar patterns of expression during both UVR and chemical skin carcinogenesis, that Slug and Snail can be differentially regulated under some conditions and that in vitro findings may not recapitulate in vivo results. View Full-Text
Keywords: slug; snail; epithelial-mesenchymal transition; skin carcinogenesis slug; snail; epithelial-mesenchymal transition; skin carcinogenesis

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Von Maltzan, K.; Li, Y.; Rundhaug, J.E.; Hudson, L.G.; Fischer, S.M.; Kusewitt, D.F. Role of the Slug Transcription Factor in Chemically-Induced Skin Cancer. J. Clin. Med. 2016, 5, 21.

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