Neoplastic transformation of a human keratinocyte cell line by the v-fos oncogene

To analyze the role of the fos oncogene in the growth of human epithelial cells, we have transfected a non-tumorigenic human epidermal keratinocyte line (RHEK-1) immortalized by the Ad12-SV40 hybrid virus with a plasmid carrying the v-fos gene together with plasmid pSV2-neo which confers resistance to neomycin. Individual neomycin-resistant clones were isolated and characterized with respect to morphological alteration. Of 16 independent clones analyzed, two appeared morphologically transformed and formed foci in culture. Only the two clones with a transformed phenotype were found by Southern blot hybridization analysis to contain the transfected v-fos gene. These clones formed colonies in soft agar and induced tumors when transplanted into nude mice. Analysis of fos specific mRNA and protein demonstrated that the transfected v-fos gene was expressed in these two clonal lines. These findings suggest that expression of the v-fos gene might facilitate the process of neoplastic transformation of human epithelial cells in culture. This appears to represent the first demonstration of the transforming potential of the v-fos gene in human cells.