An NF-κB pathway-mediated positive feedback loop amplifies Ras activity to pathological levels in mice.

ABSTRACT: Genetic mutations that give rise to active mutant forms of Ras are oncogenic and found in several types of tumor. However, such mutations are not clear biomarkers for disease, since they are frequently detected in healthy individuals. Instead, it has become clear that elevated levels of Ras activity are critical for Ras-induced tumorigenesis. However, the mechanisms underlying the production of pathological levels of Ras activity are unclear. Here, we show that in the presence of oncogenic Ras, inflammatory stimuli initiate a positive feedback loop involving NF-κB that further amplifies Ras activity to pathological levels. Stimulation of Ras signaling by typical inflammatory stimuli was transient and had no long-term sequelae in wild-type mice. In contrast, these stimuli generated prolonge

SUBMITTER: Daniluk J 

PROVIDER: S-EPMC3314459 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature