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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


  • van Hogerlinden M
  • Rozell BL
  • Ahrlund-Richter L
  • ToftgÃ¥rd R


Cancer research

Publication Data

July 15, 1999

Associated Grants


Mesh Terms

  • 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-kappa B
  • Neoplasm Proteins
  • Neoplasms, Radiation-Induced
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-rel
  • Radiation Tolerance
  • Signal Transduction
  • Skin Neoplasms
  • Transgenes