Lay Summary

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, but the mechanisms of how and why colorectal cancer develops in certain individuals with inflammatory bowel disease are poorly understood.  Previously published studies and preliminary data from our laboratory suggest a pivotal role for bacteria and disrupted signaling of tumor growth factor-beta (TGF-β), a down-regulatory growth factor, in the development of colorectal cancer.

The proposed studies will use two mutant mouse models with a propensity for inflammatory bowel disease and colorectal cancer to understand mechanisms for defective TGF-β signaling and bacterial-induced inflammation in triggering colon cancer.  The proposed studies in animal models are relevant to the human disorder because our mutant mouse models presumably represent ‘genetically susceptible’ human populations and can give insights into how bacterial infections and TGF-β are critical components in the induction of cancer.  Understanding the mechanisms behind the transitions from inflammatory disease to dysplasia to cancer will offer opportunities for disruption, therapy and prevention.