Helicobacter pylori enhances CIP2A expression and cell proliferation via JNK2/ATF2 signaling in human gastric cancer cells

Zhao,Yongxun; Li,Yumin; Han,Jian; Liu,Tao; Guan,Quanlin; Zhao,Peng; Guo,Lingyun; Liu,Kaikun; He,Dongqiang

doi:10.3892/ijmm.2014.1615

Helicobacter pylori enhances CIP2A expression and cell proliferation via JNK2/ATF2 signaling in human gastric cancer cells

Authors:
- Yongxun Zhao
- Yumin Li
- Jian Han
- Tao Liu
- Quanlin Guan
- Peng Zhao
- Lingyun Guo
- Kaikun Liu
- Dongqiang He
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Affiliations: The Second Clinical Medical School of Lanzhou University, Lanzhou, Gansu 730030, P.R. China, Department of General Surgery, The Second Hospital of Lanzhou University, Key Laboratory of Digestive System Tumors of Gansu Province, Lanzhou, Gansu 730030, P.R. China, Institute of Pathogenic Biology, School of Basic Medical Science, Lanzhou University, Lanzhou, Gansu 730000, P.R. China, Department of Surgical Oncology, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China, Department of General Surgery, The Second Hospital of Lanzhou University, Lanzhou, Gansu 730030, P.R. China
Published online on: January 7, 2014 https://doi.org/10.3892/ijmm.2014.1615
Pages: 703-710

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Abstract

Helicobacter pylori (H. pylori) infection plays an important role in the development of gastric carcinomas. Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a novel human oncoprotein that functions as an important regulator of cell growth and malignant transformation. In the present study, we aimed to investigate the potential mechanisms by which H. pylori upregulates the expression of CIP2A and the functional impact of H. pylori-induced CIP2A in gastric cancer cells. We demonstrated that infection of MKN-45 cells with H. pylori led to a marked increase in the expression of CIP2A at the mRNA and protein levels. H. pylori-induced CIP2A was associated with increased cell proliferation. In addition, H. pylori was found to activate the JNK2 pathway. Importantly, both H. pylori-induced CIP2A production and cell proliferation were partially reversed by inhibition of JNK2 signaling. Similarly, the blockade of H. pylori-induced CIP2A expression by siRNA against CIP2A also inhibited cell proliferation. Thus, H. pylori appears to stimulate the expression of CIP2A and proliferation of gastric cancer cells via JNK2 signaling. These findings suggest that H. pylori-induced upregulation of CIP2A contributes to the development and progression of gastric cancer. Further in vivo studies are warranted to explore the biological role of CIP2A and its interaction with JNK2 signaling in gastric cancer.

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