A role for NF-κB activity in skin hyperplasia and the development of keratoacanthomata in mice.

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  • Author(s): Poligone B;Poligone B; Hayden MS; Chen L; Pentland AP; Jimi E; Ghosh S
  • Source:
    PloS one [PLoS One] 2013 Aug 19; Vol. 8 (8), pp. e71887. Date of Electronic Publication: 2013 Aug 19 (Print Publication: 2013).
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
    • Publication Information:
      Original Publication: San Francisco, CA : Public Library of Science
    • Subject Terms:
      Keratoacanthoma/*metabolism ; Papilloma/*metabolism ; Skin/*pathology ; Skin Neoplasms/*metabolism ; Transcription Factor RelA/*metabolism; Amino Acid Substitution ; Animals ; Cell Proliferation ; Hyperplasia/chemically induced ; Hyperplasia/metabolism ; Keratoacanthoma/chemically induced ; Mice ; Mice, 129 Strain ; Mice, Inbred C57BL ; Mice, Knockout ; Papilloma/chemically induced ; Receptors, Tumor Necrosis Factor, Type I/deficiency ; Receptors, Tumor Necrosis Factor, Type I/genetics ; Signal Transduction ; Skin/metabolism ; Skin Neoplasms/chemically induced ; Tetradecanoylphorbol Acetate ; Transcription Factor RelA/genetics
    • Abstract:
      Background: Previous studies have implicated NF-κB signaling in both cutaneous development and oncogenesis. However, these studies have been limited in part by the lethality that results from extreme over- or under-expression of NF-κB in available mouse models. Even cre-driven tissue specific expression of transgenes, or targeted deletion of NF-κB can cause cell death. Therefore, the present study was undertaken to evaluate a novel mouse model of enhanced NF-κB activity in the skin.
      Methods: A knock-in homologous recombination technique was utilized to develop a mouse model (referred to as PD mice) with increased NF-κB activity.
      Results: The data show that increased NF-κB activity leads to hyperproliferation and dysplasia of the mouse epidermis. Chemical carcinogenesis in the context of enhanced NF-κB activity promotes the development of keratoacanthomata.
      Conclusion: Our findings support an important role for NF-κB in keratinocyte dysplasia. We have found that enhanced NF-κB activity renders keratinocytes susceptible to hyperproliferation and keratoacanthoma (KA) development but is not sufficient for transformation and SCC development. We therefore propose that NF-κB activation in the absence of additional oncogenic events can promote TNF-dependent, actinic keratosis-like dysplasia and TNF-independent, KAs upon chemical carcinogensis. These studies suggest that resolution of KA cannot occur when NF-κB activation is constitutively enforced.
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    • Grant Information:
      K08 AR055986 United States AR NIAMS NIH HHS; P30 AR058886 United States AR NIAMS NIH HHS; R37 AI033443 United States AI NIAID NIH HHS
    • Accession Number:
      0 (Receptors, Tumor Necrosis Factor, Type I)
      0 (Rela protein, mouse)
      0 (Tnfrsf1a protein, mouse)
      0 (Transcription Factor RelA)
      NI40JAQ945 (Tetradecanoylphorbol Acetate)
    • Publication Date:
      Date Created: 20130827 Date Completed: 20140408 Latest Revision: 20211021
    • Publication Date:
      20240829
    • Accession Number:
      PMC3747062
    • Accession Number:
      10.1371/journal.pone.0071887
    • Accession Number:
      23977171