| First Author | Poligone B | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 8 | Pages | e71887 |
| PubMed ID | 23977171 | Mgi Jnum | J:204921 |
| Mgi Id | MGI:5543733 | Doi | 10.1371/journal.pone.0071887 |
| Citation | Poligone B, et al. (2013) A role for NF-kappaB activity in skin hyperplasia and the development of Keratoacanthomata in mice. PLoS One 8(8):e71887 |
| abstractText | BACKGROUND: Previous studies have implicated NF-kappaB 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-kappaB in available mouse models. Even cre-driven tissue specific expression of transgenes, or targeted deletion of NF-kappaB can cause cell death. Therefore, the present study was undertaken to evaluate a novel mouse model of enhanced NF-kappaB 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-kappaB activity. RESULTS: The data show that increased NF-kappaB activity leads to hyperproliferation and dysplasia of the mouse epidermis. Chemical carcinogenesis in the context of enhanced NF-kappaB activity promotes the development of keratoacanthomata. CONCLUSION: Our findings support an important role for NF-kappaB in keratinocyte dysplasia. We have found that enhanced NF-kappaB activity renders keratinocytes susceptible to hyperproliferation and keratoacanthoma (KA) development but is not sufficient for transformation and SCC development. We therefore propose that NF-kappaB 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-kappaB activation is constitutively enforced. |
