Analysis of the rasH oncogene and its p21 product in chemically induced skin tumors and tumor-derived cell lines.

Mouse skin papillomas and squamous cell carcinomas induced by initiation with 7,12-dimethylbenz[a]anthracene and promotion with phorbol esters, such as 12-O-tetradecanoyl phorbol-13-acetate, frequently contain an activated Harvey ras gene. Six murine epidermal cells lines established from pooled skin papillomas previously tested negative in the NIH-3T3 assay, but have an altered differentiation program by a variety of criteria. The Harvey ras gene and its p21 protein product from these cell lines have been analyzed for alterations responsible for their altered growth and differentiation properties that were undetectable by 3T3 transfection assays. In comparison with primary papillomas and carcinomas, shown to have a point mutation in codon 61 of the Harvey ras gene, resulting in a p21 product with the diagnostic alteration in SDS-PAGE, the papilloma cell lines exhibited neither the codon 61 mutation, nor p21 product with altered migration in SDS-PAGE. These findings suggest that these papilloma cell lines contain a genetic lesion(s), other than Harvey ras activation, that may be responsible for their altered epithelial differentiation patterns and thus may serve as a useful model for identifying lesions involved in malignant conversion.