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Chronic exposure to both acid and bile leads to increased risk of Barrett’s oesophagus and oesophageal adenocarcinoma (OA). Bile acids can be both potent tumour promoters and carcinogens and are known to increase the expression of COX-2, which is involved in the development of Barrett’s oesophagus and OA. Song et al investigated the detailed molecular mechanisms by which bile acids regulate COX-2 expression in the oesophagus. They analysed the effects of bile acids on COX-2 expression in immortalised Barrett’s and OA cells and used several molecular techniques to identify relevant signalling pathways. Flow cytometry and reactive oxygen species (ROS) scavengers were used to examine ROS involvement. Immunohistochemistry was performed on oesophageal mucosa obtained from an established rat model of bile reflux. The authors showed that unconjugated bile acids induce cAMP response element-binding and AP-1-dependent COX-2 expression in Barrett’s oesophagus and OA through ROS-mediated activation of PI3K/AKT and ERK1/2 (see fig).
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