Fang F, Flegler AJ, Du P, Lin S, Clevenger CV: Expression of Cyclophilin B is Associated with Malignant Progression and Regulation of Genes Implicated in the Pathogenesis of Breast Cancer. Am J Pathol 2009, 174:297-308
Inflammation Contributes to Colon Cancer
Researchers led by Dr. Brian Iritani at The University of Washington found that mice that lack the immune inhibitory molecule Smad3 are acutely sensitive to both bacterially-induced inflammation and cancer. They report these findings in the January 2009 issue of The American Journal of Pathology.
Bacteria contribute to the development of certain cancers, in some measure, by stimulating chronic inflammation. Absence of a molecule that inhibits inflammation, Smad3, may therefore increase susceptibility to colon cancer.
To examine whether Smad3 signaling contributes to development of colon cancer, Maggio-Price et al examined mice deficient in Smad3 that lack of adaptive immune responses. They found that these mice are acutely sensitive to bacterially-induced inflammation and cancer due to both deficient T regulatory cell function and increased expression of proinflammatory cytokines. Through increased expression of both pro-oncogenic and anti-apoptotic proteins, epithelial cells in colonic tissues underwent both enhanced proliferation and survival.
"That the inflammatory response to microorganisms is a key event in these results reveals important 'tumor-suppressive' functions for Smad3 in T effector cells, T regulatory cells, and intestinal epithelial cells, all of which may normally limit the development of colon cancer in response to bacterial inflammation," explains Dr. Iritani's group.
Maggio-Price L, Treuting P, Bielefeldt-Ohmann H, Seamons A, Drivdahl R, Zeng W, Lai L-H, Huycke M, Phelps S, Brabb T1, Iritani BM: Bacterial infection of Smad3/Rag2 do
|Contact: Angela Colmone|
American Journal of Pathology