c-Rel downregulation affects cell cycle progression of human keratinocytes.

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.