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Gut 52:174-180 doi:10.1136/gut.52.2.174
  • Oesophagus

Upregulation of the oncogene c-myc in Barrett’s adenocarcinoma: induction of c-myc by acidified bile acid in vitro

  1. C Tselepis1,
  2. C D Morris2,
  3. D Wakelin1,
  4. R Hardy1,
  5. I Perry1,
  6. Q T Luong1,
  7. E Harper1,
  8. R Harrison4,
  9. S E A Attwood3,
  10. J A Z Jankowski5
  1. 1Epithelial Laboratory, Division of Medical Sciences, University of Birmingham, UK
  2. 2Epithelial Laboratory, Division of Medical Sciences, University of Birmingham, UK, and Department of Surgery, Hope Hospital, Manchester, UK
  3. 3Department of Surgery, Hope Hospital, Manchester, UK
  4. 4Department of Pathology, University of Birmingham, UK
  5. 5Digestive Disease Centre, University Department of Medicine and Oncology, Leicester Royal Infirmary, LE1 5WW, UK
  1. Correspondence to:
    Dr C Tselepis, Department of Medicine, University of Birmingham, Vincent Drive, Birmingham B15 2TH, UK;
    christ{at}cancer.bham.ac.uk
  • Accepted 20 August 2002

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.

Footnotes