Mouse Models of the Skin: Models to Define Mechanisms of Skin Carcinogenesis

The multistep model of mouse skin carcinogenesis has facilitated identification of irreversible genetic events of initiation and progression, and epigenetic events of tumor promotion. Mouse skin tumor initiation can be accomplished by a single exposure to a sufficiently small dose of a carcinogen, and this step is rapid and irreversible. However, promotion of skin tumor formation requires a repeated and prolonged exposure to a promoter, and that tumor promotion is reversible. Investigations focused on the mechanisms of mouse car-cinogenesis have resulted in the identifications of potential molecular targets of cancer induction and progression useful in planning strategies for human cancer prevention trials. This special issue contains eight papers that focus on mouse models used to study individual proteins expressed in the mouse skin and the role they play in differentiation, tissue homeostasis, skin carcinogenesis, and chemoprevention of skin cancer. In the paper entitled " Ap1 transcription factors in epider-mal differentiation and skin cancer, " R. Eckert et al. highlight the role of AP1, a transcription factor composed of c-jun and c-fos, that serves as a central node in epidermal keratinocyte survival and differentiation. The authors discuss how AP1 deregulation leads to key steps in driving the development of cancer and how these functions in cancer may be different in epidermal development. Finally, they summarize the various mouse models that have helped elucidate the role of this very interesting molecule. In the paper entitled " The role of TGFí µí»½ signaling in squamous cell cancer: lessons from mouse models, " A. Glick summarizes the current literature on the role of TGFí µí»½1 in normal tissues and in carcinogenesis. TGFí µí»½1 is a member of a large growth factor family including activins/inhibins and bone morphogenic proteins (BMPs) that have potent growth regulatory and immunomodulatory functions in normal skin homeostasis, regulation of epidermal stem cells, extracellular matrix production, angiogenesis, and inflammation. The author presents a thorough comparison between the role of TGFí µí»½1 in signaling in human HNSCC and cutaneous SCC and the various mouse models that have been developed to elucidate the role this molecule plays in oncogenesis. In the paper entitled " Multiple roles for VEGF in non-melanoma skin cancer: angiogenesis and beyond, " K. Johnson and T. Wilgus overview how vascular endothelial growth factor (VEGF), a potent proangiogenic factor in mouse and human skin tumors, plays a role in the development of non-melanoma skin cancers. The authors have detailed the …