ABSTRACT
This chapter describes the derivation of the in vitro multistep human epidermal keratinocyte model, the factors involved in modulating this cellular transformation system, the usefulness of this model system for viral, chemical, and radiation carcinogenesis, and the multistep nature of human epithelial cell carcinogenesis. In experiments to determine which of the transforming genes in the Ad12-SV40 hybrid virus genomes were actively transcribed in the altered human epithelial cells, molecular characterization of the RHEK-1 line was carried out. The Ki-MSV-altered RHEK-1 cells released focus-forming viruses and expressed the K-ras p21 protein. When athymic nude mice were inoculated with as few as Ki-MSV-transformed RHEK-1 cells, the animals developed invasive, rapidly progressive tumors within 3 weeks. Several investigators have reported that primary rodent fibroblasts can undergo neoplastic conversion in response to the combined action of two viral or cellular oncogenes. In an attempt to achieve maximum transformation efficiency, the effect of hydrocortisone on focus formation by Ki-MSV in human epidermal keratinocytes was examined.
