Open AccessLoss of E‐cadherin in mouse gastric epithelial cells induces signet ring‐like cells, a possible precursor lesion of diffuse gastric cancer
Author(s) -
Mimata Ayako,
Fukamachi Hiroshi,
Eishi Yoshinobu,
Yuasa Yasuhito
Publication year - 2011
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2011.01890.x
Subject(s) - cadherin , pathology , enterochromaffin like cell , gastric mucosa , biology , stromal cell , foveolar cell , signet ring cell , hyperplasia , gastric glands , cancer research , hyperplastic polyp , metaplasia , cancer cell , signet ring cell carcinoma , cancer , stomach , cell , medicine , adenocarcinoma , genetics , colorectal cancer , colonoscopy
Alterations in the E‐cadherin gene are associated with sporadic and hereditary diffuse‐type gastric cancer. To determine how the loss of function of E‐cadherin affects gastric epithelial cell phenotypes, we generated transgenic mice using the Cre‐loxP system in which the E‐cadherin gene is specifically knocked out in the parietal cell lineage. In the transgenic mice, expression of E‐cadherin was lost or reduced in proton pump‐expressing parietal cells, which became round in shape and were pushed out of the glands to accumulate in the stromal area. Additionally, gastric mucosa exhibited hyperplasia from 3 months in the mice, some cells of which later became positive for trefoil factor 2, a marker of spasmolytic polypeptide‐expressing metaplasia. From 6 months, E‐cadherin‐negative/proton pump‐negative cells appeared from the parietal cell lineage, which increased in number to form cell clusters. Moreover, signet ring‐like cells, which are morphologically similar to signet ring carcinoma cells, were found in the cell clusters from 12 months. However, no invasive gastric adenocarcinomas were found in the E‐cadherin‐deficient mice, even at 24 months or later. These data indicate that the loss of E‐cadherin induces possible pre‐cancerous lesions in the gastric mucosa but may not be sufficient for its malignant conversion. ( Cancer Sci 2011; 102: 942–950)