Keratinocyte specific Fos-deletion in K5-Sos-F mouse tumor model

Expression and function of the oncogenic transcription factor AP-1 (mainly composed of Jun and Fos proteins) is required for neoplastic transformation of mouse and human keratinocytes in vitro and tumor promotion as well as malignant progression in vivo. Here, we describe the identification of novel Fos target genes using global gene expression profiling with samples from a tumor model of mouse skin (K5-SOS-F). We could identify 366 differentially expressed genes comparing expression profiles from tumor samples of control animals with samples derived form mice with a specific deletion of fos in keratinocytes. Keywords: Fos-deletion, Fos-floxed, K5-SOS-F mouse tumor model, skin papilloma, global gene expression, microarray, Fos target in skin carcinogenesis In the present Experiment two different genotypes in combination with an established mouse tumor model were compared. An active form of the Sos (son of sevenless) is expressed under a keratin5 promoter leading to a constitutive activation of the Ras-Raf pathway, which results in skin papilloma formation. In the context of this tumor model an epidermis specific homozygote Fos-deletion was compared to homozygous floxed Fos-alleles. Both genotypes (Fos-deleted and Fos-floxed) were treated equally. The specimens were taken from skin papilloma at the mouse tail. A total number of six specimens from six different individuals (three biological replicates per genotype) were taken. Each sample was prepared and hybridized against Universal Mouse Reference RNA (Stratagene) in a dye-swap experiment, resulting in two technical replicates for each specimen, respectively.