Expression of homeobox gene CDX2 precedes that of CDX1 during the progression of intestinal metaplasia

Abstract

Background. The CDX1 and CDX2 genes are intestinal transcription factors that may be involved in the regulation of proliferation and differentiation of intestinal epithelial cells. There have been no detailed reports directly comparing the expression of CDX1 with that of CDX2 in chronic gastritis and intestinal metaplasia. Accordingly, we examined the expression of CDX1/2 and its association with the expression of other intestinal metaplasia-associated genes during the development of intestinal metaplasia. Methods. The expression of CDX1/2 genes was analyzed, using the reverse transcriptase-polymerase chain reaction, in 44 human gastric tissue samples obtained endoscopically. The expressions of mucin markers (MUC2, MUC5AC), intestine-specific genes (sucrase-isomaltase, human defensin-5, alkaline phosphatase), a gene marker for fundic gland area (H⁺/K ⁺ATPase β subunit), and a gene for entire gastric glands (pepsinogen C) were also comparatively analyzed. Results. There was no expression of CDX1/2 in gastric mucosa not infected by Helicobacter pylori. The prevalence of CDX1 mRNA expression was significantly higher in mucosa with intestinal metaplasia than in mucosa without intestinal metaplasia. It is noteworthy that CDX2 was expressed in the antral and fundic mucosa in the absence of the expression of CDX1 and gene markers for intes-tinal metaplasia. Conclusions. The expression of CDX2 precedes those of CDX1, sucrase-isomaltase, other intestine-specific genes (human defensin-5, alkaline phosphatase), and MUC2 during the progression of intestinal metaplasia. These findings imply that the expression of CDX2 may trigger the initiation and development of intestinal metaplasia.