Squamous cell carcinomas and increased apoptosis in skin with inhibited Rel/nuclear factor-kappaB signaling.
The Rel/nuclear factor-kappaB (Rel/NF-kappaB) transcription factors have been implicated previously in control of apoptosis, cell proliferation, and oncogenesis. Here we show that selective inhibition of Rel/NF-kappaB signaling in murine skin, by targeted overexpression of a super-repressor form of IkappaB-alpha, results in an increased basal frequency of apoptotic cells and the spontaneous development of squamous cell carcinomas. Presence of hyperplasia and hair follicle degeneration demonstrate an important role for Rel/NF-kappaB signaling in normal epidermal development and homeostasis. Transgenic skin, in addition, showed an enhanced sensitivity to UV-induced apoptosis. These data suggest an involvement of the Rel/NF-kappaB signaling pathway in apoptosis and cancer development of the skin.
Pubmed ID: 10416581 RIS Download
Animals | Apoptosis | Carcinoma, Squamous Cell | Crosses, Genetic | DNA-Binding Proteins | Epidermis | Gene Expression Regulation, Neoplastic | Genetic Predisposition to Disease | Hair Diseases | Hair Follicle | Hyperplasia | I-kappa B Proteins | Keratinocytes | Mice | Mice, Inbred C57BL | Mice, Inbred CBA | Mice, Transgenic | NF-KappaB Inhibitor alpha | NF-kappa B | Neoplasm Proteins | Neoplasms, Radiation-Induced | Proto-Oncogene Proteins | Proto-Oncogene Proteins c-rel | Radiation Tolerance | Signal Transduction | Skin Neoplasms | Transgenes