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INCREASED CAUDAL-RELATED HOMEOBOX GENE CDX1 EXPRESSION PRECEDES DEVELOPMENT OF INTESTINAL METAPLASIA

Although it has been recognised for many years that reflux of bile into the oesophagus is associated with the development of Barrett’s oesophagus, the precise mechanism has been unclear. Cdx1 and Cdx2 genes code for intestinal specific transcription factors that govern the differentiation of intestinal epithelial cells during development. When expressed in the stomach, Cdx1 induces gastric epithelial cells to differentiate to intestinal type cells. This study used a rat model of Barrett’s oesophagus, in which the oesophagus was re-implanted into the upper jejunum. This exposes the oesophagus to bile reflux and intestinal metaplasia develops over a period of 6 months. At 2 months, there was increased expression of Cdx1 and at 6 months, 30% had developed columnar lined epithelium, which stained for both Cdx1 and Cdx2 proteins. In vitro bile acids induced expression of Cdx1 in both adenocarcinoma and the normal oesophageal cell line in a dose–response fashion (see fig). Transfection of a normal oesophageal cell line Het-1A with Cdx1 increased Cdx2 promoter activity and the authors suggest that Cdx1 may mediate the expression of Cdx2, which in turn leads to the development of Barrett’s metaplasia.

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Bile acids increase expression of Cdx1 protein.

SERUM PEPSINOGENS: RISK FACTORS FOR GASTRIC BUT NOT OESOPHAGEAL CANCERS

Atrophy of the gastric fundic mucosa is considered to be a risk factor for gastric cancer. It has also been suggested that chronic atrophic gastritis might be a risk factor for oesophageal squamous cell carcinoma. Low …

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