Identification of genes and gene ontology processes critical to skin papilloma development in Tg.AC transgenic mice

This study analyzes gene expression associated with papilloma development in Tg.AC v-Ha-ras transgenic mice and identifies novel genes and biological processes that may be critical to skin carcinogenesis in these mice. Epidermal abrasion was used to synchronously induce epidermal regeneration in FVB/N wild type and transgenic Tg.AC mice. Skin papillomagenesis was uniquely induced in Tg.AC mice, and gene expression profiling was carried out using a 22 000 element mouse DNA microarray. Histological analysis showed that papillomas developed at a high rate by d 30 after abrasion in transgenic animals, while no papilloma developed in wild type mice. Transgene-specific differentially expressed genes were identified at d 30 postabrasion and these genes were annotated using EASE software and literature mining. Annotated and non-annotated genes associated with papilloma development were identified and clustering analysis revealed groups of genes that are coordinately expressed. A number of genes associated with differentiation and development were also physically clustered on mouse chromosome 16, including 16B3 that contains several Stefins and stefin-like genes, and 16A1 containing a number of keratin associated protein genes. Additional analyses presented here yield novel insights into the genes and processes involved in papilloma development in Tg.AC mice.