| First Author | Zur R | Year | 2015 |
| Journal | Oncotarget | Volume | 6 |
| Issue | 15 | Pages | 12920-35 |
| PubMed ID | 26079427 | Mgi Jnum | J:291951 |
| Mgi Id | MGI:6448515 | Doi | 10.18632/oncotarget.4320 |
| Citation | Zur R, et al. (2015) Combined deletion of p38gamma and p38delta reduces skin inflammation and protects from carcinogenesis. Oncotarget 6(15):12920-35 |
| abstractText | The contribution of chronic skin inflammation to the development of squamous cell carcinoma (SCC) is poorly understood. While the mitogen-activated protein kinase p38alpha regulates inflammatory responses and tumour development, little is known about the role of p38gamma and p38delta in these processes. Here we show that combined p38gamma and p38delta (p38gamma/delta) deletion blocked skin tumour development in a chemically induced carcinogenesis model. p38gamma/delta deletion reduced TPA-induced epidermal hyperproliferation and inflammation; it inhibited expression of proinflammatory cytokines and chemokines in keratinocytes in vitro and in whole skin in vivo, resulting in decreased neutrophil recruitment to skin. Our data indicate that p38gamma/delta in keratinocytes promote carcinogenesis by enabling formation of a proinflammatory microenvironment that fosters epidermal hyperproliferation and tumourigenesis. These findings provide genetic evidence that p38gamma and p38delta have essential roles in skin tumour development, and suggest that targeting inflammation through p38gamma/delta offers a therapeutic strategy for SCC treatment and prevention. |
