Antitumor activity of the MEK inhibitor trametinib on intestinal polyp formation in Apc(Δ716) mice involves stromal COX-2.

ABSTRACT: Extracellular signal-regulated kinase is an MAPK that is most closely associated with cell proliferation, and the MEK/ERK signaling pathway is implicated in various human cancers. Although epidermal growth factor receptor, KRAS, and BRAF are considered major targets for colon cancer treatment, the precise roles of the MEK/ERK pathway, one of their major downstream effectors, during colon cancer development remain to be determined. Using Apc(Δ716) mice, a mouse model of familial adenomatous polyposis and early-stage sporadic colon cancer formation, we show that MEK/ERK signaling is activated not only in adenoma epithelial cells, but also in tumor stromal cells including fibroblasts and vascular endothelial cells. Eight-week treatment of Apc(Δ716) mice with trametinib, a small-molecule MEK i

SUBMITTER: Fujishita T 

PROVIDER: S-EPMC4471789 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature