Details

Autor(en) / Beteiligte

• Takasu, Shinji
• Tsukamoto, Tetsuya
• Cao, Xue‐Yuan
• Toyoda, Takeshi
• Hirata, Akihiro
• Ban, Hisayo
• Yamamoto, Masami
• Sakai, Hiroki
• Yanai, Tokuma
• Masegi, Toshiaki
• Oshima, Masanobu
• Tatematsu, Masae

Titel

Roles of cyclooxygenase‐2 and microsomal prostaglandin E synthase‐1 expression and β‐catenin activation in gastric carcinogenesis in N‐methyl‐N‐nitrosourea‐treated K19‐C2mE transgenic mice

Ist Teil von

• Cancer science, 2008-12, Vol.99 (12), p.2356-2364

Ort / Verlag

Melbourne, Australia: Blackwell Publishing Asia

Erscheinungsjahr

2008

Quelle

MEDLINE

Beschreibungen/Notizen

• K19‐C2mE transgenic (Tg) mice, simultaneously expressing cyclooxygenase‐2 (COX‐2) and microsomal prostaglandin E synthase‐1 (mPGES‐1) in the gastric mucosa under the cytokeratin 19 gene promoter, were here treated with N‐methyl‐N‐nitrosourea (MNU) and inoculated with Helicobacter pylori (H. pylori) to investigate gastric carcinogenesis. Wild‐type (WT) and Tg mice undergoing MNU treatment frequently developed tumors in the pyloric region (100% and 94.7%, respectively); multiplicity in Tg was higher than that in WT (P < 0.05) with H. pylori infection. Larger pyloric tumors were more frequently observed in Tg than in WT (P < 0.05). In addition, Tg developed fundic tumors, where WT did not. No gastric tumors were observed without MNU treatment. Transcripts of TNF‐α, iNOS, IL‐1β, and CXCL14 were up‐regulated with H. pylori infection in both genotypes and were also increased more in Tg than in WT within H. pylori‐inoculated animals. Immunohistochemical analysis demonstrated significantly greater β‐catenin accumulation in pyloric tumors, compared with those in the fundus (P < 0.01) with mutations of exon 3; 18.2% and 31.6% in MNU‐alone and MNU + H. pylori‐treated WT, whereas 21.4% and 62.5% was observed in the Tg, respectively; the latter significantly higher (P < 0.05), suggesting the role of H. pylori in Wnt activation. In conclusion, K19‐C2mE mice promoted gastric cancer in both fundic and pyloric regions. Furthermore β‐catenin activation may play the important role of pyloric carcinogenesis especially in H. pylori‐infected Tg. Induction of various inflammatory cytokines in addition to overexpression of COX‐2/mPGES‐1 could be risk factors of gastric carcinogenesis and may serve as a better gastric carcinogenesis model. (Cancer Sci 2008; 99: 2356–2364)