Upregulation of the oncogene c-myc in Barrett's adenocarcinoma: induction of c-myc by acidified bile acid in vitro. Issue 2 (1st February 2003)

• Record Type: Journal Article
• Authors: Tselepis, C; Morris, C D; Wakelin, D; Hardy, R; Perry, I; Luong, Q T; Harper, E; Harrison, R; Attwood, S E A; Jankowski, J A Z
• Is Part Of: Gut. Volume 52:Issue 2(2003)
• Page Start: 174
• Page End: 180
• Publication Date: 2003-02-01
• Subjects: c-myc -- Barrett's metaplasia -- bile acid; GORD, gastro-oesophageal reflux disease -- DCA, deoxycholic acid -- CDCA, chenodeoxycholic acid -- PCR, polymerase chain reaction -- Ct, cycle threshold -- ESA, epithelial cell specific antigen; Gastroenterology -- Periodicals; 616.33
• DOI: 10.1136/gut.52.2.174
• Languages: English
• ISSNs: 0017-5749

Abstract

Abstract : Background and aims: C-myc over expression is implicated in malignancy although to date this has not been studied in Barrett's metaplasia. We sought to determine c-myc expression in the malignant progression of Barrett's metaplasia and whether it may be induced by bile acids seen in gastro-oesophageal refluxate. Methods: C-myc protein and mRNA levels were assessed in 20 Barrett's metaplasia and 20 oesophageal adenocarcinoma samples by western blotting and real time polymerase chain reaction. Levels of c-myc and proliferation were also assessed in cell lines OE21, OE33, SW-480, and TE-7 stimulated with pulses or continuous exposure to the bile acids deoxycholic acid and chenodeoxycholic acid. Results: C-myc protein was upregulated in 50% of Barrett's metaplasia and 90% of oesophageal adenocarcinoma samples compared with squamous, gastric, and duodenal controls. C-myc immunolocalisation in Barrett's metaplasia revealed discrete nuclear localisation, becoming more diffuse with progression from low to high grade dysplasia to adenocarcinoma. Both continual and pulsed bile acid induced c-myc at pH 4, with no effect at pH 7 or with acidified media alone. Pulsed bile acid treatment induced proliferation (p<0.05); in contrast, continuous exposure led to suppression of proliferation (p<0.05). Conclusions: We have shown upregulation of c-myc with malignant progression of Barrett's metaplasia and suggest that acidified bile may be a novel agent responsible for induction of this oncogene.