Peroxisome Proliferator-activated Receptor β (δ)-dependent Regulation of Ubiquitin C Expression Contributes to Attenuation of Skin Carcinogenesis
| Autor: | Dae Joon Kim, Taro E. Akiyama, Jeffrey M. Peters, Weiwei Shan, Frank J. Gonzalez, Mary J. Kennett, F. S. Harman, Jerrold M. Ward, Amanda M. Burns |
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| Rok vydání: | 2004 |
| Předmět: |
Skin Neoplasms
Molecular Sequence Data Receptors Cytoplasmic and Nuclear Peroxisome proliferator-activated receptor medicine.disease_cause Biochemistry Mice Ubiquitin medicine Animals Cloning Molecular Promoter Regions Genetic Receptor Ubiquitin C Molecular Biology chemistry.chemical_classification Reporter gene Base Sequence biology Microarray analysis techniques Cell Biology Molecular biology Cell biology Gene Expression Regulation Neoplastic Cell Transformation Neoplastic chemistry Mutagenesis Site-Directed biology.protein Tumor promotion Carcinogenesis Cell Division Transcription Factors |
| Zdroj: | Journal of Biological Chemistry. 279:23719-23727 |
| ISSN: | 0021-9258 |
| Popis: | The role of peroxisome proliferator-activated receptor-beta (PPARbeta) in the molecular regulation of skin carcinogenesis was examined. Increased caspase-3 activity associated with apoptosis was found in the skin of wild-type mice after tumor promotion with 12-O-tetradecanoylphorbol-13-acetate, and this effect was diminished in PPARbeta-null mice. The onset of tumor formation, tumor size, and tumor multiplicity induced from a two-stage carcinogen bioassay (7,12-dimethylbenz[a]anthracene/12-O-tetradecanoylphorbol-13-acetate) were significantly enhanced in PPARbeta-null mice compared with wild-type mice. To begin to characterize the molecular changes underlying this PPARbeta-dependent phenotype, microarray analysis was performed and a number of differentially regulated gene products were identified including ubiquitin C. Subsequent promoter analysis, reporter gene assays, site-directed mutagenesis, and electrophoretic mobility shift assays provide evidence that PPARbeta regulates ubiquitin C expression, and that ubiquitination of proteins is influenced by PPARbeta. These results strongly suggest that activation of PPARbeta-dependent target genes provides a novel strategy to inhibit tumor promotion and carcinogenesis. |
| Databáze: | OpenAIRE |
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