TITLE

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

AUTHOR(S)
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.
PUB. DATE
February 2003
SOURCE
Gut;Feb2003, Vol. 52 Issue 2, p174
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background and aims: C-myc over expression is implicated in malignancy although to date this has not been studied in Barrett's metaplosia. 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 immunoIocalisation in Barrett's metaplasia revealed discrete nuclear Iocalisation, becoming more diffuse with progression from Iow 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.
ACCESSION #
9704703

 

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