The inflammatory response and tumorigenesis in the absence of the MAP3K8 gene

Skin cancer is the most common form of cancer in the United States, with more than one million cases diagnosed annually. Inflammation is believed to be a critical component to skin cancer progression, and therefore understanding genes that control inflammation is highly desirable. MAP3K8 (Tpl2) is a protein kinase in the MAPK signal transduction cascade. It has previously been shown that mice that lack MAP3K8 (Tpl2 -/- mice) have significantly higher tumor incidence and inflammation than wild-type (WT) controls. My thesis investigated the mechanism behind these effects by using inhibitors specific to the p38, JNK, PKC, and NF-kappaB pathways. Western blot analysis revealed differences in p38, JNK and NF-kappaB pathway activity between the WT and Tpl2 -/- mouse primary keratinocytes. In vivo experiments confirmed these differences and illustrated that the NF-kappaB pathway is the primary pathway responsible for the increased incidence of inflammation and tumorigenesis observed in Tpl2 -/- mice.