2 ONCOGENES, V-FOS AND V-RAS, COOPERATE TO CONVERT NORMAL KERATINOCYTES TO SQUAMOUS-CELL CARCINOMA

Previous studies have implicated the ras(Ha) oncogene in the initiation of skin carcinogenesis and the fos oncogene in malignant progression of premalignant skin cell lines. To determine if these two oncogenes are sufficient to convert normal keratinocytes to cancer cells, freshly isolated mouse keratinocytes were coinfected with replication-defective (ψ-2) v-ras(Ha) and v-fos viruses in culture. When tested in nude mice within several days of infection, v-fos/v-ras(Ha)-coinfected keratinocytes produced squamous cell carcinomas. Introduction of v-fos alone resulted in normal or hyperplastic skin, whereas v-ras(Ha) alone produced squamous papillomas. These results inducate that two oncogenes are sufficient to produce the malignant phenotype in epidermal cells. Furthermore, they clearly link the fos oncogene with malignant conversion. Since fos acts as a transcriptional regulator of other genes, malignant conversion may be an indirect consequence of the overexpression of the fos-encoded protein leading to a change in the expression of fos-controlled cellular genes.