Interacting Signaling Pathways in Mouse Skin Tumor Initiation and Progression
The multistage induction of squamous cell cancer (SCC) on mouse skin as a consequence of chemical exposures has remarkable phenotypic and genotypic homology to human SCC development. Genetically altered mouse models have been instrumental in defining the respective contribution of signaling pathways on the development of SCC in vivo. Central to the skin carcinogenesis process is the activation of the EGFR-Ras-MAPK pathway. While hyperactivation of the pathway can often be attributed to activating mutations in ras genes, it appears that for the majority of cases the pathway is activated by alterations in upstream modulators as well as downstream effectors that are integral to the altered phenotype of the initiated keratinocytes. This chapter will review data from experimental inductions of cutaneous SCC with a special emphasis on mouse models. Particularly, the role of the EGFR-Ras-MAPK pathway, protein kinase C, nuclear factor kappa B and the expression of proinflammatory factors by transformed keratinocyte will be covered in more detail.
KeywordsEpidermal Growth Factor Receptor KRAS Mutation Squamous Cell Carcinoma Epidermal Growth Factor Receptor Inhibitor Skin Carcinogenesis
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