A Role for NF-kappa B Activity in Skin Hyperplasia and the Development of Keratoacanthomata in Mice

作者：Poligone Brian^*; Hayden Matthew S; Chen Luojing; Pentland Alice P; Jimi Eijiro; Ghosh Sankar

来源：PLos One, 2013, 8(8): e71887.

DOI：10.1371/journal.pone.0071887

Background: Previous studies have implicated NF-kappa B 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-kappa B in available mouse models. Even cre-driven tissue specific expression of transgenes, or targeted deletion of NF-kappa B can cause cell death. Therefore, the present study was undertaken to evaluate a novel mouse model of enhanced NF-kappa B 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-kappa B activity.
Results: The data show that increased NF-kappa B activity leads to hyperproliferation and dysplasia of the mouse epidermis. Chemical carcinogenesis in the context of enhanced NF-kappa B activity promotes the development of keratoacanthomata.
Conclusion: Our findings support an important role for NF-kappa B in keratinocyte dysplasia. We have found that enhanced NF-kappa B activity renders keratinocytes susceptible to hyperproliferation and keratoacanthoma (KA) development but is not sufficient for transformation and SCC development. We therefore propose that NF-kappa B 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-kappa B activation is constitutively enforced.

• 出版日期2013-8-19