Gene Set: DURCHDEWALD_SKIN_CARCINOGENESIS_UP

Standard name DURCHDEWALD_SKIN_CARCINOGENESIS_UP
Systematic name M1683
Brief description Genes up-regulated upon skin specific knockout of FOS [GeneID=2353] by cre-lox in the K5-SOS-F mice (express a constitutively active form of SOS1 [GeneID=6654] in the skin).
Full description or abstract Expression and function of the oncogenic transcription factor activator protein (AP-1; mainly composed of Jun and Fos proteins) is required for neoplastic transformation of keratinocytes in vitro and tumor promotion as well as malignant progression in vivo. Here, we describe the identification of 372 differentially expressed genes comparing skin tumor samples of K5-SOS-F transgenic mice (Fos(f/f) SOS(+)) with samples derived from animals with a specific deletion of c-Fos in keratinocytes (Fos(Deltaep) SOS(+)). Fos-dependent transcription of selected genes was confirmed by quantitative real-time PCR analysis using tumor samples and mouse back skin treated with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). One of the most differentially expressed genes encodes the small mucin-like glycoprotein Podoplanin (Pdpn), whose expression correlates with malignant progression in mouse tumor model systems and human cancer. We found Pdpn and Fos expression in chemically induced mouse skin tumors, and detailed analysis of the Pdpn gene promoter revealed impaired activity in Fos-deficient mouse embryonic fibroblasts, which could be restored by ectopic Fos expression. Direct Fos protein binding to the Pdpn promoter was shown by chromatin immunoprecipitation and a TPA-induced complex at a TPA-responsive element-like motif in the proximal promoter was identified by electrophoretic mobility shift assays. In summary, we could define a Fos-dependent genetic program in a well-established model of skin tumors. Systematic analysis of these novel target genes will guide us in elucidating the molecular mechanisms of AP-1-regulated pathways that are critically implicated in neoplastic transformation and/or malignant progression.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 18757399   Authors: Durchdewald M,Guinea-Viniegra J,Haag D,Riehl A,Lichter P,Hahn M,Wagner EF,Angel P,Hess J
Exact source Table 1S
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Organism Mus musculus
Contributed by Jessica Robertson (MSigDB Team)
Source platform MOUSE_GENE_SYMBOL
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Version history 3.1: First introduced

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