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

Brian Poligone, Matthew S. Hayden, Luojing Chen, Alice P. Pentland, Eijiro Jimi, Sankar Ghosh

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish
Article numbere71887
JournalPLoS One
Volume8
Issue number8
DOIs
Publication statusPublished - Aug 19 2013
Externally publishedYes

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Keratoacanthoma
hyperplasia
Hyperplasia
Skin
animal models
keratinocytes
carcinogenesis
mice
Chemical activation
hyperkeratosis
Keratinocytes
homologous recombination
Cell death
Carcinogenesis
transgenes
cell death
Actinic Keratosis
Tissue
Homologous Recombination
Transgenes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

A role for NF-κB activity in skin hyperplasia and the development of keratoacanthomata in mice. / Poligone, Brian; Hayden, Matthew S.; Chen, Luojing; Pentland, Alice P.; Jimi, Eijiro; Ghosh, Sankar.

In: PLoS One, Vol. 8, No. 8, e71887, 19.08.2013.

Research output: Contribution to journalArticle

Poligone, Brian ; Hayden, Matthew S. ; Chen, Luojing ; Pentland, Alice P. ; Jimi, Eijiro ; Ghosh, Sankar. / A role for NF-κB activity in skin hyperplasia and the development of keratoacanthomata in mice. In: PLoS One. 2013 ; Vol. 8, No. 8.
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