| First Author | Kim C | Year | 2014 |
| Journal | EMBO Mol Med | Volume | 6 |
| Issue | 7 | Pages | 970-83 |
| PubMed ID | 24952939 | Mgi Jnum | J:232288 |
| Mgi Id | MGI:5776445 | Doi | 10.15252/emmm.201303541 |
| Citation | Kim C, et al. (2014) Epidermal p65/NF-kappaB signalling is essential for skin carcinogenesis. EMBO Mol Med 6(7):970-83 |
| abstractText | The nuclear factor kappa B (NF-kappaB) signalling pathway exhibits both tumour-promoting and tumour-suppressing functions in different tissues and models of carcinogenesis. In particular in epidermal keratinocytes, NF-kappaB signalling was reported to exert primarily growth inhibitory and tumour-suppressing functions. Here, we show that mice with keratinocyte-restricted p65/RelA deficiency were resistant to 7, 12-dimethylbenz(a)anthracene (DMBA)-/12-O-tetra decanoylphorbol-13 acetate (TPA)-induced skin carcinogenesis. p65 deficiency sensitized epidermal keratinocytes to DNA damage-induced death in vivo and in vitro, suggesting that inhibition of p65-dependent prosurvival functions prevented tumour initiation by facilitating the elimination of cells carrying damaged DNA. In addition, lack of p65 strongly inhibited TPA-induced epidermal hyperplasia and skin inflammation by suppressing the expression of proinflammatory cytokines and chemokines by epidermal keratinocytes. Therefore, p65-dependent NF-kappaB signalling in keratinocytes promotes DMBA-/TPA-induced skin carcinogenesis by protecting keratinocytes from DNA damage-induced death and facilitating the establishment of a tumour-nurturing proinflammatory microenvironment. |
