Journal of Gastrointestinal Surgery

, Volume 11, Issue 7, pp 827–834

The Pathogenesis of Barrett’s Esophagus: Secondary Bile Acids Upregulate Intestinal Differentiation Factor CDX2 Expression in Esophageal Cells

  • Yingchuan Hu
  • Valerie A. Williams
  • Oliver Gellersen
  • Carolyn Jones
  • Thomas J. Watson
  • Jeffrey H. Peters
Article

DOI: 10.1007/s11605-007-0174-3

Cite this article as:
Hu, Y., Williams, V.A., Gellersen, O. et al. J Gastrointest Surg (2007) 11: 827. doi:10.1007/s11605-007-0174-3

Abstract

Introduction

Clinical evidence strongly suggests that bile acids are important in the development of Barrett’s esophagus, although the mechanism remains unknown. Caudal-related homeobox 2 (CDX2) is a transcription factor recently implicated in early differentiation and maintenance of normal intestinal epithelium and is suggested to play a key role in the pathogenesis of intestinal metaplasia in Barrett’s esophagus.

Objective

The aim of this study was to investigate the effect of primary and secondary bile acids on CDX2 mRNA expression in human esophageal cells.

Methods

Human esophageal cells: (1) squamous, immortalized by SV40 (Het-1A); (2) adenocarcinoma (SEG-1); and (3) squamous cell carcinoma (HKESC-1 & HKESC-2), were exposed in cell culture for 1–24 h to 100–1,000 μM deoxycholic, chenodeoxycholic, and glycocholic acids. Total RNA was extracted before and after bile acid treatment and reverse transcribed to cDNA. CDX2 mRNA expression was determined by both quantitative real-time and reverse transcription PCR (RT-PCR).

Results

CDX2 mRNA expression was absent before bile acid exposure in all cell lines. CDX2 expression increased in a dose- and time-dependent fashion with deoxycholic and chenodeoxycholic, but not glycocholic, acid in all four cell lines. The maximal induction of CDX2 expression was seen in SEG-1 adenocarcinoma cells. Expression in Het-1A cells also increased significantly as did expression in HKESC-1,2 cells, although to a lesser extent than in adenocarcinoma.

Conclusions

These findings show that secondary bile acid stimulation upregulates CDX2 gene expression in both normal and cancer cell lines. They further support the role of bile acids in the pathogenesis of Barrett’s esophagus and link the clinical evidence of a high prevalence of luminal bile acids in Barrett’s to expression of the gene thought to be responsible for the phenotypic expression of intestinal metaplasia.

Keywords

Barrett’s esophagus Gastroesophageal reflux disease (GERD) Caudal-related homeobox 2 (CDX2) 

Copyright information

© The Society for Surgery of the Alimentary Tract 2007

Authors and Affiliations

  • Yingchuan Hu
    • 1
  • Valerie A. Williams
    • 1
  • Oliver Gellersen
    • 1
  • Carolyn Jones
    • 1
  • Thomas J. Watson
    • 1
  • Jeffrey H. Peters
    • 1
  1. 1.Department of Surgery, School of Medicine and DentistryUniversity of RochesterRochesterUSA

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