Conditional ablation of C/EBPβ demonstrates its keratinocyte-specific requirement for cell survival and mouse skin tumorigenesis
| Autor: | Songyun Zhu, R C Smart, José L. Jorcano, E Sterneck, Angel Ramirez |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Keratinocytes
Cancer Research Cell type Skin Neoplasms 9 10-Dimethyl-1 2-benzanthracene Cre recombinase Apoptosis Biology medicine.disease_cause Article Mice Enhancer binding Keratin Genetics medicine Animals Promoter Regions Genetic Molecular Biology Mice Knockout chemistry.chemical_classification Integrases integumentary system Keratin-15 CCAAT-Enhancer-Binding Protein-beta Molecular biology Mice Inbred C57BL Keratin 5 medicine.anatomical_structure chemistry Carcinogens Keratin-5 Keratins Tetradecanoylphorbol Acetate Female Keratinocyte Carcinogenesis |
| Zdroj: | Oncogene. 25:1272-1276 |
| ISSN: | 1476-5594 0950-9232 |
| DOI: | 10.1038/sj.onc.1209144 |
| Popis: | The CCAAT/enhancer binding protein beta (C/EBP beta) is implicated in the regulation of many different molecular and physiological processes. Mice with a germline deletion of C/EBP beta (C/EBP beta(-/-)) display phenotypes in a multitude of cell types and organ systems, including skin where C/EBP beta(-/-) mice exhibit increased apoptosis in epidermal keratinocytes in response to carcinogen treatment and are completely resistant to carcinogen-induced skin tumorigenesis. To determine the contribution of systemic versus cell autonomous functions of C/EBP beta to specific phenotypes, mice with a conditional 'floxed' C/EBP beta null allele were generated. Epidermal-specific deletion of C/EBP beta was achieved by Cre recombinase expression from a keratin 5 (K5) promoter. Similar to C/EBP beta(-/-) mice, K5-Cre;C/EBP beta(fl/fl) mice were completely refractory to 7,12 dimethylbenz[a]anthracene (DMBA)-induced skin tumorigenesis and these mice displayed increased DMBA-induced apoptosis in epidermal keratinocytes compared to wild-type mice. In contrast, mice lacking the related gene, C/EBP delta, were not resistant to DMBA-induced skin tumorigenesis, indicating a unique role of C/EBP beta in skin tumor development. Our findings demonstrate that C/EBP beta exerts an essential, keratinocyte-intrinsic role in cell survival in response to carcinogen treatment and the elimination of C/EBP beta in keratinocytes is sufficient to confer complete resistance of the skin to chemical carcinogenesis. |
| Databáze: | OpenAIRE |
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