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.
van Hogerlinden
M
M
Department of Bioscience at Novum, Karolinska Institute, NOVUM, Huddinge, Sweden.
Rozell
B L
BL
Ahrlund-Richter
L
L
Toftgård
R
R
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology*; D003433:Crosses, Genetic; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D004817:Epidermis / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006201:Hair Diseases / Q000235:genetics / Q000473:pathology; D018859:Hair Follicle / Q000473:pathology; D006965:Hyperplasia; D020672:I-kappa B Proteins; D015603:Keratinocytes / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D009363:Neoplasm Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D009381:Neoplasms, Radiation-Induced / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D020569:Proto-Oncogene Proteins c-rel; D011836:Radiation Tolerance / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D012878:Skin Neoplasms / Q000235:genetics / Q000473:pathology*; D019076:Transgenes
D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B; D009363:Neoplasm Proteins; C000606205:Nfkbia protein, mouse; D011518:Proto-Oncogene Proteins; D020569:Proto-Oncogene Proteins c-rel; D000072000:NF-KappaB Inhibitor alpha