Conditional Ablation of C/Ebp Beta Demonstrates Its Keratinocyte-specific Requirement for Cell Survival and Mouse Skin Tumorigenesis.
From: Molecular Mechanisms in Development Group, Laboratory of Protein Dynamics and Signaling, National Cancer Institute, Frederick, MD , USA.
Oncogene
- Publish Date: Feb 2006
- ISSN: 0950-9232
- Volume: 25
- Issue: 8
- Pages: 1272-6
- Medium: Print
- Language: English
- Citation (JAMA): Sterneck E, Zhu S, Ramirez A, et al. Conditional Ablation of C/Ebp Beta Demonstrates Its Keratinocyte-specific Requirement for Cell Survival and Mouse Skin Tumorigenesis.. Oncogene Feb 2006;25:1272-6
Abstract
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.
Mesh Headings (Keywords): 9,10-Dimethyl-1,2-benzanthracene, Animals, Apoptosis, CCAAT-Enhancer-Binding Protein-beta, Carcinogens, Female, Integrases, Keratin-5, Keratinocytes, Keratins, Mice, Mice, Inbred C57BL, Mice, Knockout, Promoter Regions (Genetics), Skin Neoplasms, Tetradecanoylphorbol Acetate
Check for Full Text / PubMed Unique Identifier (PMID): 16205634
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