Models of esophageal carcinogenesis.

Attempting to formulate a model for the development of esophageal cancer, we have undertaken three interrelated projects: (1) identification and characterization of stem cells as a basis to understand lineage specification in the normal esophageal squamous epithelium and possibly transdifferentiation into an intestinal metaplastic phenotype that defines Barrett's esophagus; (2) elucidation of the role of epidermal growth factor receptor and signaling mechanisms in proliferation and transformation in squamous cell carcinoma; and (3) modeling transformation in organotypic culture, a 3-dimensional culture system, as a platform for investigating epithelial-stromal interactions. It is hoped that development of these models for carcinogenesis will permit formulation of effective chemoprevention, diagnostic, and therapeutic strategies.