| 共同演者 |
Imatani Akira（Division of Gastroenterology, Tohoku University School of Medicine, Japan）, Asano Naoki（Division of Gastroenterology, Tohoku University School of Medicine, Japan）, Fushiya Jun（Division of Gastroenterology, Tohoku University School of Medicine, Japan）, Jin XiaoYi（Division of Gastroenterology, Tohoku University School of Medicine, Japan）, Chiba Takashi（Division of Gastroenterology, Tohoku University School of Medicine, Japan）, Endo Hiroyuki（Division of Gastroenterology, Tohoku University School of Medicine, Japan）, Ara Nobuyuki（Division of Gastroenterology, Tohoku University School of Medicine, Japan）, Koike Tomoyuki（Division of Gastroenterology, Tohoku University School of Medicine, Japan）, Iijima Katsunori（Division of Gastroenterology, Tohoku University School of Medicine, Japan）, Shimosegawa Tooru（Division of Gastroenterology, Tohoku University School of Medicine, Japan） |
| 抄録 |
Background ＆ Aim：Helicobacter pylori（H.pylori）infection is well known to induce intestinal-type gastric cancer through the trans-differentiation to intestinal metaplasia. We previously reported that a homeobox gene Sox2 is down-regulated while a pseuokinase Tribble 3（Trib3）is induced during this trans-differentiation. We aimed to clarify the mechanism of gastric carcinogenesis by Trib3. Methods ＆ Results：Quantitative real-time PCR revealed that H.pylori infection increased Trib3 expression up to 27.0±1.96 folds in a murine normal gastric epithelial cell line GSM06, and to 1.43±0.31 folds in the gastric mucosa of C57BL/6J mice. Promoter reporter assay, as well as western blotting using NF-κB inhibitor BAY11-7082, indicated that this induction was dependent on NF-κ. We then developed the GSM06 cells stably over-expressing Trib3（Trib3GSM06）for further analyses. In MTT assay and spheroid colony forming assay, Trib3GSM06 cells displayed increased proliferation and colony forming ability. On the other hand, H.pylori infection induced phosphorylation of a tyrosine phosphatase SHP-2 in a time dependent manner, and this phosphorylation was greatly enhanced to 1.42 folds in Trib3 GSM06. Moreover, the number of cells expressing hummingbird phenotype was significantly greater in Trib3GSM06. Conclusions：Our study suggested that H.pylori infection induces Trib3 via activation of NF-κ, which leads to gastric carcinogenesis through the activation of SHP-2. |
