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Conditional ablation of C/EBPβ demonstrates its keratinocyte-specific requirement for cell survival and mouse skin tumorigenesis

Oncogene volume 25, pages 1272–1276 (2006)Cite this article

Abstract

The CCAAT/enhancer binding protein β (C/EBPβ) is implicated in the regulation of many different molecular and physiological processes. Mice with a germline deletion of C/EBPβ (C/EBPβ−/−) display phenotypes in a multitude of cell types and organ systems, including skin where C/EBPβ−/− 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/EBPβ to specific phenotypes, mice with a conditional ‘floxed’ C/EBPβ null allele were generated. Epidermal-specific deletion of C/EBPβ was achieved by Cre recombinase expression from a keratin 5 (K5) promoter. Similar to C/EBPβ−/− mice, K5-Cre;C/EBPβfl/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/EBPδ, were not resistant to DMBA-induced skin tumorigenesis, indicating a unique role of C/EBPβ in skin tumor development. Our findings demonstrate that C/EBPβ exerts an essential, keratinocyte-intrinsic role in cell survival in response to carcinogen treatment and the elimination of C/EBPβ in keratinocytes is sufficient to confer complete resistance of the skin to chemical carcinogenesis.

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Acknowledgements

We would like to thank Dr Peter Johnson for his scientific input; Barbara Shankle and Daniel Logsdon for expert technical assistance; Dr Lino Tessarollo for β-actin-cre mice and help with generating the C/EBPβfl/+ mice and Drs Mac Law and Phillip Sannes for their help with histological identification of pulmonary macrophages. This work was supported in part by National Cancer Institute Grant CA46637 (to RCS).

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  1. E Sterneck and S Zhu: These authors contributed equally to this manuscript.

Authors and Affiliations

  1. Molecular Mechanisms in Development Group, Laboratory of Protein Dynamics and Signaling, National Cancer Institute, Frederick, MD, USA

    E Sterneck & R C Smart

  2. Department of Environmental & Molecular Toxicology, Cell Signaling and Cancer Group, North Carolina State University, Raleigh, NC, USA

    S Zhu

  3. Epithelial Damage, Repair and Tissue Engineering Program, CIEMAT, Madrid, Spain

    A Ramirez & J L Jorcano

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  1. E Sterneck
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  2. S Zhu
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Correspondence to R C Smart.

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Sterneck, E., Zhu, S., Ramirez, A. et al. Conditional ablation of C/EBPβ demonstrates its keratinocyte-specific requirement for cell survival and mouse skin tumorigenesis. Oncogene 25, 1272–1276 (2006). https://doi.org/10.1038/sj.onc.1209144

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