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

<p>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.</p>