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Updated: May 9, 2026

Generation and Culturing of Primary Human Keratinocytes from Adult Skin
Published on: December 22, 2017
c-Rel downregulation affects cell cycle progression of human keratinocytes
Verena N Lorenz1, Michael P Schön1, Cornelia S Seitz1
1Department of Dermatology, Venereology and Allergology, Georg August University Göttingen, Göttingen, Germany.
Abstract:
The c-Rel protein, a member of the NF-κB transcription factor family, exerts unique and distinctive functions in various cell types. Although c-Rel is expressed in human epidermis, its functions in keratinocytes are poorly understood. Our small interfering RNA-based approach of c-Rel silencing in HaCaT keratinocytes induced altered cell morphology toward a spindle-shaped appearance. In addition, c-Rel downregulation resulted in increased apoptosis and significantly reduced proliferation towing to G2/M cell cycle delay, concomitant aberrant mitotic spindle formation, and induction of phospho-aurora A(Thr288). The relevance of c-Rel in epithelial carcinogenesis was further supported by detection of c-Rel expression in squamous cell carcinomas of the skin. Our studies indicate that c-Rel is a key regulator of cell fate decisions in keratinocytes such as cell growth and death and may have a role in epidermal carcinogenesis.
Insights
The c-Rel protein regulates keratinocyte cell fate, impacting growth and death. Its downregulation in skin cells leads to altered morphology, increased apoptosis, and reduced proliferation, suggesting a role in skin cancer.
Area of Science:
- Molecular Biology
- Cell Biology
- Dermatology
Background:
- c-Rel, a transcription factor in the NF-κB family, has distinct functions across cell types.
- Its role in human epidermal keratinocytes remains largely uncharacterized.
Purpose of the Study:
- To investigate the function of c-Rel in keratinocytes.
- To determine the role of c-Rel in epidermal carcinogenesis.
Main Methods:
- Utilized small interfering RNA (siRNA) to silence c-Rel in HaCaT keratinocytes.
- Analyzed cell morphology, apoptosis, proliferation, cell cycle progression, and mitotic spindle formation.
Main Results:
- c-Rel silencing induced spindle-shaped morphology and increased apoptosis.
- Downregulation of c-Rel led to reduced proliferation, G2/M cell cycle delay, aberrant mitotic spindle formation, and elevated phospho-aurora A (Thr288).
- c-Rel expression was detected in skin squamous cell carcinomas.
Conclusions:
- c-Rel is a critical regulator of keratinocyte cell fate, controlling cell growth and death.
- c-Rel plays a significant role in epidermal carcinogenesis.
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