title: c-Rel downregulation affects cell cycle progression of human keratinocytes.
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.
authors.affiliation: Department of Dermatology, Venereology and Allergology, Georg August University Göttingen, Göttingen, Germany.
authors.forename: Verena N
authors.initials: VN
authors.lastname: Lorenz
authors.affiliation: Department of Dermatology, Venereology and Allergology, Georg August University Göttingen, Göttingen, Germany.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Schön
authors.affiliation: Department of Dermatology, Venereology and Allergology, Georg August University Göttingen, Göttingen, Germany. Electronic address: cseitz@med.uni-goettingen.de.
authors.forename: Cornelia S
authors.initials: CS
authors.lastname: Seitz
mesh_terms: D017209:Apoptosis / Q000502:physiology; D001913:Bowen's Disease / Q000473:pathology / Q000503:physiopathology; D002294:Carcinoma, Squamous Cell / Q000473:pathology* / Q000503:physiopathology; D002453:Cell Cycle / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D002461:Cell Line, Transformed; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000502:physiology; D000078404:Epidermal Cells; D004817:Epidermis / Q000502:physiology; D016195:G2 Phase / Q000502:physiology; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology*; D055623:Keratosis, Actinic / Q000473:pathology / Q000503:physiopathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D020569:Proto-Oncogene Proteins c-rel; D034741:RNA, Small Interfering / Q000235:genetics; D012878:Skin Neoplasms / Q000473:pathology* / Q000503:physiopathology
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D020569:Proto-Oncogene Proteins c-rel; C068059:REL protein, human; D034741:RNA, Small Interfering
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