Our recent study on the rat model and human Barrett's esophagus have suggested squamous de-differentiation (i.e., loss of squamous transcription factors, p63, sox2) and columnar differentiation (i.e., gain of intestinal transcription factors, Cdx1, Cdx2, GATA4, HNF1α) were two essential aspects of intestinal metaplasia [38]. This evidence concerns the gene GATA4 and esophageal adenocarcinoma.