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

The ras proto-oncogene family products are membrane-associated, guanine nuc leotide-binding proteins that serve as a molecular switch for signal transd uction pathways in a diverse array of organisms. In the mouse skin two-stag e carcinogenesis model, a specific point mutation in Ha-ras codon 61 is res ponsible for the initiation event. Here we investigated whether Ha-ras prot ein and mRNA expression change during premalignant progression. Also, we as sessed the Ha-ras mutated allele after these changes. To those ends, we ana lysed the Ha-ras expression profiles in normal and hyperplastic skin, papil lomas, and squamous cell carcinomas by western blotting, reverse transcript ion-polymerase chain reaction, and in situ hybridization. increased levels of Ha-ras expression were observed at specific times during promotion. Thes e 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 progress ion. (C) 1999 Wiley-Liss, Inc.