Squamous Cell Carcinomas and Increased Apoptosis in Skin with Inhibited Rel/Nuclear Factor-κB Signaling

The Rel/nuclear factor-κB (Rel/NF-κB) transcription factors have been implicated previously in control of apoptosis, cell proliferation, and oncogenesis. Here we show that selective inhibition of Rel/NF-κB signaling in murine skin, by targeted overexpression of a super-repressor form of IκB-α, 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-κB 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-κB signaling pathway in apoptosis and cancer development of the skin.