Increased expression of mutated Ha-ras during premalignant progression in SENCAR mouse skin.

The ras proto-oncogene family products are membrane-associated, guanine nucleotide-binding proteins that serve as a molecular switch for signal transduction pathways in a diverse array of organisms. In the mouse skin two-stage carcinogenesis model, a specific point mutation in Ha-ras codon 61 is responsible for the initiation event. Here we investigated whether Ha-ras protein and mRNA expression change during premalignant progression. Also, we assessed the Ha-ras mutated allele after these changes. To those ends, we analysed the Ha-ras expression profiles in normal and hyperplastic skin, papillomas, and squamous cell carcinomas by western blotting, reverse transcription-polymerase chain reaction, and in situ hybridization. Increased levels of Ha-ras expression were observed at specific times during promotion. These changes were followed by an increase in the level of expression of the Ha-ras mutated allele. These results suggest that increased expression of Ha-ras mutated alleles may have an important role during premalignant progression. Copyright 1999 Wiley-Liss, Inc.