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Carcinogenesis Advance Access published online on September 24, 2007
Carcinogenesis, 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 TGFß1 and its Role in Skin Carcinogenesis

Adam Glick1,#, Rolando Perez-Lorenzo1,2 and Javed Mohammed1

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

# corresponding author, 201 Life Sciences Bld, The Pennsylvania State University, University Park, PA 16801 abg11{at}psu.edu

TGFß1 signaling plays a critical role in skin carcinogenesis. While most studies have focused on TGFß1 signaling and response in keratinocytes it is now becoming clear that the interaction of keratinocyte derived TGFß1 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 proinflammatory and immunosuppressive actions of TGFß1 on tumor development. Indeed the paradigm of TGFß1 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 TGFß1 on carcinogenesis in the skin and other epithelial tissues.

Key Words: Transforming growth factor ß1 • Smad • Papilloma • Squamous cell carcinoma • Inflammation • Immunosurveillance • Two-stage skin carcinogenesis

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


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