Expression of Cdx1 and Cdx2 mRNAs and relevance of this expression to differentiation in human gastrointestinal mucosa--with special emphasis on participation in intestinal metaplasia of the human stomach.
BACKGROUND
The caudal-type homeobox genes, Cdx1 and Cdx2, are candidates for directing intestinal development, differentiation, and maintenance of the intestinal phenotype. The aims of this study were: (1) to assess the normal tissue expression patterns of Cdx1 and Cdx2 in the human gastrointestinal tract and (2) to ascertain levels in intestinal metaplasia (IM) of the stomach associated with gastritis.


METHODS
Fresh human tissues were collected by surgical resection from 39 patients after informed consent had been received. RNAs were extracted from 11 distinct sites in the gastrointestinal mucosa (gastric body, gastric antrum, duodenum, jejunum, ileum, cecum, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum), and Northern hybridization was performed for Cdr1 and Cdx2 mRNAs. In addition, RNAs were also extracted from normal gastric mucosa, and gastric mucosa with mild to severe IM, confirmed histopathologically. Reverse-transcriptase polymerase chain reaction (RT-PCR) was then carried out for Cdx1 and Cdx2.


RESULTS
The expression of Cdx1 mRNA increased gradually from the duodenum to the distal colon, with no expression detected in the stomach. Compared with the distribution of Cdx1 mRNA in the mouse gastrointestinal tract, the expression of Cdr1 mRNA in the human gastrointestinal tract showed greater predominance in the jejunum and ileum. The expression of Cdx2 mRNA increased gradually from the duodenum to the proximal colon and decreased from the ascending colon to the rectum. Compared with the expression pattern of Cdx2 mRNA in the mouse gastrointestinal tract, the expression of Cdx2 mRNA in the human gastrointestinal tract showed greater predominance in the ileum. By RT-PCR, both Cdx1 and Cdx2 mRNAs were detected in the mild and severe types of IM. However, neither of these mRNAs was identified in normal gastric mucosa without IM.


CONCLUSIONS
Cdr1 and Cdx2 mRNAs are widely present in the human intestinal and colonic mucosae, but not in the gastric mucosa, suggesting that their expression may contribute to the intestinal phenotype. The high levels of these mRNAs in IM mucosa associated with chronic atrophic gastritis point to an association with this phenotypic shift in the gastric mucosa.
Mizoshita
T
T
Division of Oncological Pathology, Aichi Cancer Center Research Institute, Nagoya, Japan.
Inada
K
K
Tsukamoto
T
T
Kodera
Y
Y
Yamamura
Y
Y
Hirai
T
T
Kato
T
T
Joh
T
T
Itoh
M
M
Tatematsu
M
M
D000328:Adult; D000368:Aged; D015152:Blotting, Northern; D000071616:CDX2 Transcription Factor; D002454:Cell Differentiation; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D005757:Gastritis, Atrophic / Q000235:genetics; D005770:Gastrointestinal Neoplasms / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008679:Metaplasia; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013270:Stomach / Q000473:pathology*; D015534:Trans-Activators / Q000235:genetics
C491273:CDX1 protein, human; D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; C491272:Cdx1 protein, mouse; D017931:DNA Primers; D018398:Homeodomain Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D015534:Trans-Activators