目的： 探讨幽门螺旋杆菌细胞毒素相关基因A（cytotoxin associated gene A，CagA）与胃黏膜中TET2（ten-eleven translocation 2）蛋白表达的关系，以及TET2在CagA致癌过程中可能的作用。 方法： Real-time PCR检测人胃黏膜上皮细胞株GES-1和胃癌细胞株MGC-803中 TET2 b mRNA 的表达水平，细胞免疫染色法检测TET2 蛋白的细胞定位及表达。将pEGFP-CagA通过脂质体介导转染GES-1细胞，用200 μmol/L H2O2处理GES-1 细胞建立氧化应激模型，流式细胞仪检测细胞中活性氧（reactive oxygen species, ROS）和细胞周期的变化。 结果： TET2 mRNA 在GES-1细胞的表达水平低于胃癌MGC-803细胞(1.00±0.08 vs 1.68±0.07，P<005)，TET2蛋白在GES-1细胞表达水平低于胃癌MGC-803细胞 (8.09±3.57 vs 14.60±2.31，P<0.05)。与阴性对照组pEGFP-N1相比，pEGFP-CagA转染组GES-1细胞中 TET2 mRNA表达水平升高 (1.00±004 vs 0.06±0.00， P<0.05)，TET2蛋白表达水平也升高(16.45±4.40 vs 10.82±3.39，P<0.05)，ROS积累水平升高(18.39±4.52 vs 1531±440，P<0.05)，细胞周期检测出现明显的凋亡峰。氧化应激(H2O2处理)模型中GES-1细胞与空白对照GES-1细胞相比， TET2 mRNA水平升高(1.44±0.02 vs 1.00±0.04，P<0.05)，TET2蛋白表达水平增高 (15.72±452 vs 11.74±4.34，P<0.05)。 结论： 幽门螺旋杆菌毒力因子CagA可诱导GES-1细胞ROS增高和细胞周期的失衡，氧化应激可以诱导TET2表达上调，TET2可能参与CagA的致癌过程。

Objective: To investigate the association between the expression of the ten-eleven translocation 2 (TET2) protein and the cytotoxin associated gene A (CagA) of Helicobacter pylori (Hp)，and to explore the possible mechanisms of CagA in the process of gastric carcinogenesis. Methods: Real-time PCR was used to detect TET2 mRNA level in human gastric epithelial GES-1 cells and gastric cancer MGC-803 cells. Immuncytochemistry was used to detect the TET2 protein localization and expression in GES-1 and MGC-803 cells. GES-1 cells were transfected with pEGFP-CagA and a cell oxidative stress model was constructed with 200 μmol/L H2O2. Flow cytometry was used to analyze cell cycle and ROS in GES-1 cells. Results: The mean expression level of TET2 mRNA in GES-1 cells was lower than that in MGC-803 cells (1.00±0.08 vs 1.68±0.07, P<0.05). TET2 protein expression in GES-1 cells was lower than that in MGC-803 cells (8.09±3.57 vs 14.60±2.31，P<0.05). Compared with the negative control pEGFP-N1 group, the mean expression level of TET2 mRNA in pEGFP-CagA-transfected GES-1 cells was increased (1.00±0.04 vs 0.06±000，P<005), and TET2 protein expression in pEGFP-CagA-transfected GES-1 cells was also increased (10.82±3.39 vs 16.45±4.40，P<0.05), and a higher level of ROS production was observed in pEGFP-CagA-transfected GES-1 cells (69±90 vs 91±16.8，P<0.05), which significantly displayed the cell apoptosis in cycle analysis. In the cell oxidative stress model, TET2 mRNA level in H2O2 treated cells was higher than that in normal GES-1 cells (1.44±0.02 vs 1.00±0.04，P<005) and TET2 protein expression level was higher than that in normal GES-1 cells (11.74±4.34 vs 15.72±452，P<0.05). Conclusion: CagA factor can induce ROS accumulation and cell cycle disruption of GES-1, indicating that TET2 can be upregulated by oxidative stress and may be involved in the progress of CagA-induced carcinogenesis.

国家重点基础研究发展计划（973计划）资助项目（No. 2010CB933901），国家杰出青年基金资助项目（No. 81225010）