| First Author | Decicco-Skinner KL | Year | 2011 |
| Journal | Oncogene | Volume | 30 |
| Issue | 4 | Pages | 389-97 |
| PubMed ID | 20935675 | Mgi Jnum | J:168812 |
| Mgi Id | MGI:4938258 | Doi | 10.1038/onc.2010.447 |
| Citation | Decicco-Skinner KL, et al. (2011) Loss of tumor progression locus 2 (tpl2) enhances tumorigenesis and inflammation in two-stage skin carcinogenesis. Oncogene 30(4):389-97 |
| abstractText | Tumor progression locus 2 (Tpl2) is a serine/threonine kinase in the mitogen-activated protein kinase signal transduction cascade known to regulate inflammatory pathways. Previously identified as an oncogene, its mutation or overexpression is reported in a variety of human cancers. To address its role in skin carcinogenesis, Tpl2(-/-) or wild-type (WT) C57BL/6 mice were subjected to a two-stage dimethylbenzanthracene/12-O-tetradecanoylphorbol-13-acetate (TPA) mouse skin carcinogenesis model. Tpl2(-/-) mice developed a significantly higher incidence of tumors (80%) than WT mice (17%), as well as a reduced tumor latency and a significantly higher number of total tumors (113 vs 6). Moreover, Tpl2(-/-) mice treated with TPA experienced significantly higher nuclear factor kappaB (NF-kappaB) activation, edema, infiltrating neutrophils and production of proinflammatory cytokines than did WT mice. We investigated the role of the p38, JNK, MEK and NF-kappaB signaling pathways both in vitro and in vivo in WT and Tpl2(-/-) mice by using inhibitors for each of these pathways. We confirmed that the proinflammatory effect in Tpl2(-/-) mice was due to heightened activity of the NF-kappaB pathway. These studies indicate that Tpl2 may serve more as a tumor suppressor than as an oncogene in chemically induced skin carcinogenesis, with its absence contributing to both tumorigenesis and inflammation. |
