Basic–alimentary tractCarcinogenesis in Mouse Stomach by Simultaneous Activation of the Wnt Signaling and Prostaglandin E2 Pathway
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Tissue Samples
In total, 80 patients were preoperatively diagnosed with sporadic gastric cancer (47 intestinal type and 33 diffuse type) in 1998–1999 at Kanazawa University Hospital, Japan. Any patients with signet ring cell carcinoma were excluded because of the difficulty in evaluating nuclear β-catenin staining. All experiments were carried out according to the protocol approved by the Ethics Committee of Kanazawa University. Informed consent was obtained from all participants.
Transgenic Mice
The K19 promoter with a
Activation of the Wnt Pathway in Human Gastric Cancer Tissues
We first examined 80 cases of gastric cancer (47 and 33 cases for the intestinal type and diffuse type, respectively) by immunohistochemistry (Figure 1). The nuclear localization of β-catenin was detected in 24 and 19 cases of intestinal-type and diffuse-type gastric cancer, respectively, whereas β-catenin was found in the basolateral membrane of the adjacent normal tissues of the same patients (Figure 1B, C, E and F). These results suggest that the Wnt pathway is activated in 54% of the
Discussion
Wnt signaling plays an important role in the maintenance of the intestinal crypt containing the stem cells and undifferentiated progenitor cells.14, 15 In the gastric gland, Wnt signaling also keeps the progenitor cells undifferentiated in the isthmus of the gastric gland because we have shown that the number of progenitors increased significantly in the K19-Wnt1 mouse stomach. It has been reported that Wnt signal activation was found in 30% of the human gastric cancer examined.4 In the present
References (24)
- et al.
Regulation of prostaglandin E2 biosynthesis by inducible membrane-associated prostaglandin E2 synthase that acts in concert with cyclooxygenase-2
J Biol Chem
(2000) - et al.
Suppression of intestinal polyposis in ApcΔ716 knockout mice by inhibition of cyclooxygenase 2 (COX-2)
Cell
(1996) - et al.
Prostaglandin E2 promotes colorectal adenoma growth via transactivation of the nuclear peroxisome proliferator-activated receptor δ
Cancer Cell
(2004) Wnt signaling in disease and in development
Cell Res
(2005)- et al.
Loss of Apc heterozygosity and abnormal tissue building in nascent intestinal polyps in mice carrying a truncated Apc gene
Proc Natl Acad Sci U S A
(1995) - et al.
Intestinal polyposis in mice with a dominant stable mutation of the β-catenin gene
EMBO J
(1999) - et al.
β-Catenin mutation is a frequent cause of Wnt pathway activation in gastric cancer
Cancer Res
(2002) Helicobacter pylori infection and gastric cancer
Cancer Epidemiol Biomarkers Prev
(2003)- et al.
Hyperplastic gastric tumors induced by activated macrophages in COX-2/mPGES-1 transgenic mice
EMBO J
(2004) - et al.
Inducible microsomal prostaglandin E synthase is overexpressed in colorectal adenomas and cancer
Clin Cancer Res
(2001)
Colorectal cancer prevention and treatment by inhibition of cyclooxygenase-2
Nat Rev Cancer
Cyclooxygenase-2 expression and effect of celecoxib in gastric adenomas of trefoil factor 1-deficient mice
Cancer Res
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2021, Best Practice and Research: Clinical GastroenterologyCitation Excerpt :In line with the findings above are those obtained in the K19-Wnt1/C2mE (also called Gan) mouse model of gastric carcinogenesis [41]. These transgenic animals express Wnt1, COX-2, and PGE2 in the gastric mucosa, and develop gastric tumours with histological features resembling those of the human intestinal-type gastric cancer [42]. Gan mice raised under GF conditions develop significantly smaller tumours than SPF-Gan mice.
Supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (to H.O., M.M.T. and M.O.) and the Uehara Memorial Foundation (to H.O.).