Constitutive expression of ErbB-2 in gallbladder epithelium results in development of adenocarcinoma

Overexpression of ErbB-2 in the basal layer of biliary tract epithelium led to the development of gallbladder adenocarcinoma in 100% of transgenic mic e by 3 months of age. In addition, tumors developed in other parts of the b iliary tree (e.g., cholangiocarcinoma). Adenocarcinoma of the gallbladder a ppeared to arise via a stepwise process involving hyperplasia, adenoma form ation, and then adenocarcinoma formation. Increased ErbB-2/epidermal growth factor receptor heterodimer formation, activation of mitogen-activated pro tein kinase, and up-regulation of cyclooxygenase-2 levels (mRNA and protein ) were observed in gallbladder epithelium of these mice. These mice represe nt a unique new animal model for studying biliary tract carcinogenesis.