The Role of Proprotein Convertases in Animal Models of Skin Carcinogenesis

Many proprotein convertases (PC), especially furin and PACE4, are involved in pathological processes such as viral infection, inflammation, hypercholesterolemia, and cancer, and have been postulated as therapeutic targets for some of these diseases. In this chapter, we review mostly our work using animal models of squamous cancers that have been induced by chemical or UV carcinogenesis protocols to highlight the role of PCs in the development and progression of experimental tumors. After demonstrating in wild type mice the role of PACE4 in tumor progression as well as detecting the expression of PACE4 and furin in human non-melanoma skin cancers, we developed transgenic mice that over-express either PACE4 or furin in squamous epithelia, including the epidermis. This was accomplished by targeting the expression of the corresponding PC by using the promoter of the bovine keratin 5. Both K5-PACE4 and K5-Furin transgenic mice showed increased susceptibility to a two-stage carcinogenesis protocol of c...