Expression of the intestine-specific transcription factors, Cdx1 and Cdx2, correlates shift to an intestinal phenotype in gastric cancer cells.
OBJECTIVE
It is well known that gastric cancers (GCs) at early stages, independent of the histological type, mainly consist of gastric phenotype malignant cells, while those at advanced stage tend to have a more intestinal phenotype with progression. However, the connection between this shift and expression of homeobox genes, which are important factors to maintain tissue character, has remained unclear. We therefore evaluated the expression of Cdx1/2 in relation to the phenotype of GCs.


METHODS
We analyzed the expression of Cdx1/2 mRNAs by Northern blotting and Cdx2 protein by immunohistochemistry in seventy advanced GCs, and evaluated phenotypically using mucin- and immunohistochemistry.


RESULTS
Seventy GCs were divided phenotypically into 16 gastric (G type), 18 gastric and intestinal mixed (GI type), 18 intestinal (I type), and 18 null (N type) phenotypes, independent of the histological classification. Cdx1 and Cdx2 mRNAs statistically demonstrated an increase with shift from G to I ( P=0.042 and P=0.0082, respectively). Cdx2 nuclear staining was observed immunohistochemically in the intestinal phenotypic cancer cells, but could not be detected in those with only the gastric phenotype.


CONCLUSIONS
These results show that Cdx1 and Cdx2 might be indispensable for intestinal phenotypic expression even in gastric cancer cells.
Mizoshita
Tsutomu
T
Division of Oncological Pathology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, 464-8681 Nagoya, Japan.
Inada
Ken-ichi
K
Tsukamoto
Tetsuya
T
Nozaki
Koji
K
Joh
Takashi
T
Itoh
Makoto
M
Yamamura
Yoshitaka
Y
Ushijima
Toshikazu
T
Nakamura
Shigeo
S
Tatematsu
Masae
M
D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D015152:Blotting, Northern; D000071616:CDX2 Transcription Factor; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000032:analysis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D007422:Intestines; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis; D013274:Stomach Neoplasms / Q000737:chemistry*; D015534:Trans-Activators; D014157:Transcription Factors / Q000032:analysis*; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; C491273:CDX1 protein, human; D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors