Scientific Abstract

Proposal No.   IBD-0106
Principal Investigator:  Lillian Maggio-Price, V.M.D., Ph.D.
Applicant Organization:   University of Washington (Seattle, U.S.A.)
Project Title:  Molecular mechanism of colon carcinogenesis:  collaborative effects of Helicobacter infection and TGF-β dysregulation
Period of Award:  May 1, 2004 – November 30, 2006

Patients with Crohn's disease and ulcerative colitis are at increased risk of developing colorectal cancer.  The underlying mechanisms by which chronic and relapsing intestinal inflammation progresses to dysplasia and neoplasia are poorly understood.  Defects in Transforming Growth Factor-beta (TGF-β) and its signaling may be critical in this process.  There is accumulating evidence for a critical growth inhibitory role of TGF-b on colonic epithelial cells and a close association between abnormalities in TGF-β signaling and colon and gastric carcinogenesis.  Recent evidence further suggests a collaborative effect of bacterial infections and TGF-β signaling abnormalities in the carcinogenic process.  The molecular mechanisms underlying the collaborative effects are not understood.  The proposed studies will use two mutant mouse models with a propensity for colonic inflammation, dysplasia, and neoplasia to evaluate the molecular mechanisms of the collaborative effects of changes in TGF-β signaling and Helicobacter-induced inflammation in colonic carcinogenesis.