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Updated: Aug 15, 2026
Cell Population Analyses During Skin Carcinogenesis
Published on: August 21, 2013
Conditional ablation of C/EBP beta demonstrates its keratinocyte-specific requirement for cell survival and mouse
E Sterneck1, S Zhu2, A Ramirez3
1Molecular Mechanisms in Development Group, Laboratory of Protein Dynamics and Signaling, National Cancer Institute, Frederick, MD, USA.
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.
Insights
CCAAT/enhancer binding protein beta (C/EBP beta) is crucial for skin cell survival against carcinogens. Eliminating C/EBP beta in skin cells completely prevents chemical-induced skin tumors, highlighting its essential role in cancer resistance.
Area of Science:
- Molecular biology
- Cancer research
- Dermatology
Background:
- CCAAT/enhancer binding protein beta (C/EBP beta) regulates diverse molecular and physiological processes.
- C/EBP beta knockout mice show altered phenotypes, including increased skin cell apoptosis and resistance to skin tumors.
- The specific role of C/EBP beta in skin carcinogenesis requires further investigation.
Purpose of the Study:
- To elucidate the cell-autonomous function of C/EBP beta in epidermal keratinocytes regarding skin tumorigenesis.
- To determine if epidermal-specific deletion of C/EBP beta confers resistance to chemical carcinogens.
- To compare the role of C/EBP beta with C/EBP delta in skin tumor development.
Main Methods:
- Generation of conditional 'floxed' C/EBP beta null mice.
- Epidermal-specific deletion of C/EBP beta using keratin 5 (K5) promoter-driven Cre recombinase.
- Assessment of skin tumorigenesis and apoptosis in response to 7,12 dimethylbenz[a]anthracene (DMBA) treatment.
Main Results:
- K5-Cre;C/EBP beta(fl/fl) mice were completely resistant to DMBA-induced skin tumorigenesis.
- Epidermal keratinocytes in these mice exhibited increased apoptosis following DMBA treatment.
- Mice lacking C/EBP delta were not resistant to DMBA-induced skin tumorigenesis, indicating a unique role for C/EBP beta.
Conclusions:
- C/EBP beta plays an essential, keratinocyte-intrinsic role in cell survival following carcinogen exposure.
- The absence of C/EBP beta in epidermal cells is sufficient to confer complete resistance to chemical carcinogenesis.
- C/EBP beta is a critical factor in skin's response to chemical carcinogens and tumor development.
