Abstract

change was determined as the ratio of the level of gene expression in treated cells to that in untreated control cells grown in parallel. Results: NES-B10T cells treated with A+B for 30 weeks were round and aggregated in clumps (columnar morphological features), whereas untreated cells were spindle-shaped and dispersed (squamous features). Treated NES-B10T cells showed increased expression of CDX2 (11-fold), SOX9 (238-fold), villin (2-fold) and Cox-2 (1,310-fold). Treated NES-B10T cells also showed increased immunofluorescence for mAb DAS-1, (P< 0.04), and also for CK8 (P< 0.02). Immunofluorescence for CK4 is decreased. In contrast to these changes observed in NES-B10T squamous cells (derived from a patient with BE), NES-G2T cells (derived from a patient who had GERD without BE) exhibited no morphological, gene expression or immunofluorescence changes after 30 weeks of A+B treatment. Conclusion: Esophageal squamous cells exposed repeatedly to acid and bile salts in vitro exhibit columnar differentiation typical of Barrett's metaplasia. This finding is novel and supports the hypothesis that BE results from reflux-induced transdifferentiation or transcommitment of native esophageal cells. The absence of these changes in similarlytreated squamous cells from a patient who had GERD without BE suggest that certain host genetic factors, in addition to acid and bile reflux, are required for the development of Barrett's metaplasia.

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