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Carcinogenesis Advance Access originally published online on September 24, 2007
Carcinogenesis 2008 29(1):9-14; doi:10.1093/carcin/bgm215
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© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Context-dependent regulation of cutaneous immunological responses by TGFβ1 and its role in skin carcinogenesis

Adam B. Glick1,*, Rolando Perez-Lorenzo1,2 and Javed Mohammed1

1 Department of Veterinary and Biomedical Sciences, Center for Molecular Toxicology and Carcinogenesis, Life Sciences Building, The Pennsylvania State University, University Park, PA 16801, USA
2 Centro de Investigaciones en Enfermedades Tropicales, Universidad Autonoma de Campeche, Campeche, 24030, Mexico

* To whom correspondence should be addressed. Tel: +814 865 7170; Fax: +814 863 1696;Email: abg11{at}psu.edu

Transforming growth factor β1 (TGFβ1) signaling plays a critical role in skin carcinogenesis. While most studies have focused on TGFβ1 signaling and response in keratinocytes, it is now becoming clear that the interaction of keratinocyte-derived TGFβ1 with cells of the immune system has an equally important role in tumor development. Tumors form within the context of innate and adaptive immune responses and studies in skin and skin carcinogenesis models have provided important insight into the impact of context-dependent pro-inflammatory and immunosuppressive actions of TGFβ1 on tumor development. Indeed, the paradigm of TGFβ1 duality is clearly evident in its ability to both promote and inhibit inflammatory responses. Recent studies have begun to shed new light on the molecular basis for these actions and to provide insight into how these may contribute to context-dependent effects of TGFβ1 on carcinogenesis in the skin and other epithelial tissues.

Abbreviations: DC, dendritic cell; DMBA, 7-12-dimethylbenz[a]anthracene; IL, interleukin; LC, Langerhans cells; NK, natural killer; SCC, squamous cell carcinoma; TGFβ1, transforming growth factor β1; Th, T helper cell; TNF{alpha}, tumor necrosis factor-{alpha}; TPA, 12-O-tetradecanoylphorbol-13-acetate; Treg, regulatory T cell

Received August 20, 2007; revised September 13, 2007; accepted September 15, 2007.


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