Pathogenesis of Barrett esophagus - Deoxycholic acid up-regulates goblet-specific gene MUC2 in concert with CDX2 in human esophageal cells

Hypothesis: Bile acid exposure can. induce caudal-related homeobox 2 (CDX2) messenger RNA (mRNA) expression, a transcription factor that plays a crucial role in the development of Barrett esophagus. We investigated mucin 2 (MUC2) and CDX2 mRNA expression before and after treatment with deoxycholic acid in 4 human esophageal cell lines. Design, Setting, and Participants: Four human esophageal cell lines-(1) normal squamous cells immortalized by SV40 (Het-1A), (2) adenocarcinoma. (SEG-1), and (3 and 4) squamous cell carcinoma (HKESC-1 and HKESC-2)-were exposed in culture for 1 to 24 hours to 100 mu M to 1000 mu M deoxycholic acid. Total RNA was extracted before and after bile acid treatment and reverse transcribed to complementary DNA. Main Outcome Measure: MUC2 and CDX2 mRNA expression as determined by semiquantitative reverse transcription-polymerase chain reaction. Results: MUC2 mRNA expression was absent before deoxycholic acid exposure in all 4 cell lines. MUC2 expression increased in a dose- and time-dependent manner with deoxycholic acid in all cell lines. Deoxycholic acid activated MUC2 up-regulation, which correlated directly with CDX2 up-regulation in all 4 cell lines. Conclusions: Bile acids up-regulate both intestinal differentiation factor CDX2 and goblet cell-specific gene MUC2 in normal esophageal and cancer cell lines. Further, bile acid-stimulated MUC2 up-regulation correlates directly with CDX2 up-regulation. The simultaneous up-regulation of both CDX2 and MUC2 after bile acid exposure provides molecular evidence of the role of bile acid in the pathogenesis of Barrett esophagus.