A positive feedback loop between STAT3 and cyclooxygenase‐2 gene may contribute to Helicobacter pylori‐associated human gastric tumorigenesis. Issue 9 (1st November 2013)

• Record Type: Journal Article
• Authors: Xiong, Hua; Du, Wan; Sun, Tian‐Tian; Lin, Yan‐Wei; Wang, Ji‐Lin; Hong, Jie; Fang, Jing‐Yuan
• Is Part Of: International journal of cancer. Volume 134:Issue 9(2014:May 01)
• Page Start: 2030
• Page End: 2040
• Publication Date: 2013-11-01
• Subjects: Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.28539
• Languages: English
• ISSNs: 0020-7136

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Persistent infection with <italic>Helicobacter pylori</italic> (<italic>H. pylori</italic>) contributes to gastric diseases including chronic gastritis and gastric cancer. However, the pathogenesis of this carcinogenic bacterium has not been completely elucidated. Here, we report that <italic>H. pylori</italic> rapidly triggers STAT3 signaling and induces STAT3‐dependent COX‐2 expression both <italic>in vitro</italic> and <italic>in vivo</italic>. STAT3 upregulats COX‐2 by binding to and increasing the activity of <italic>COX‐2</italic> promoter. COX‐2 in turn regulates IL‐6/STAT3 signaling under basal conditions and during <italic>H. pylori</italic> infection. These findings suggest that a positive feedback loop between STAT3 and COX‐2 exists in the basal condition and <italic>H. pylori</italic> infectious condition. Immunohistochemical staining revealed that <italic>H. pylori</italic>‐positive gastritis tissues exhibited markedly higher levels of pSTAT3<sup>Tyr705</sup> than <italic>H. pylori</italic>‐negative ones. High pSTAT3<sup>Tyr705</sup> levels are correlated with intestinal metaplasia and dysplasia, suggesting pSTAT3<sup>Tyr705</sup> may be useful in the early detection of gastric tumorigenesis. Additionally, a strong positive correlation between STAT3/pSTAT3<sup>Tyr705</sup> levels and COX‐2 expression was identified in gastritis and gastric cancer tissues. Together, these findings provide new evidence for a positive feedback loop between STAT3 signaling and COX‐2 in <italic>H. pylori</italic> pathogenesis and may lead to new approaches for early detection and effective therapy of gastric cancer.</p> </abstract>