Jiang Ping, Yu Guoyu, Zhang Yong, Xiang Yang, Zhu Zhu, Feng Weiyang, Lee Wenhui, Zhang Yun
Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, P.R. China ; Department of Pathology and Pathophysiology, Kunming Medical University, Kunming, Yunnan 650500, P.R. China.
Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, P.R. China ; Department of Biochemistry, Kunming Medical University, Kunming, Yunnan 650500, P.R. China.
Oncol Lett. 2014 May;7(5):1525-1531. doi: 10.3892/ol.2014.1904. Epub 2014 Feb 21.
Trefoil factor 2 (TFF2) plays a protective role in gastric mucosa and may be involved in the progression of gastric cancer, but the detailed functions and underlying molecular mechanisms are not clear. The present study used a combination of clinical observations and molecular methods to investigate the correlation between abnormal expression of TFF2 and gastric cancer progression. TFF2 expression was evaluated by reverse transcription polymerase chain reaction (RT-PCR), quantitative PCR (qPCR), and western blot and immunohistochemistry analyses. TFF2 methylation levels were analyzed by genomic bisulfite sequencing method. The results showed that TFF2 mRNA and protein expression were decreased in gastric cancer tissues compared with the matched non-cancerous mucosa, and the decreased level was associated with the differentiation and invasion of gastric cancer. Moreover, the average TFF2 methylation level of CpG sites in the promoter region was 70.4% in three gastric cancer tissues, while the level in associated non-neoplastic tissues was 41.0%. Furthermore, the promoter hypermethylation of TFF2 was also found in gastric cancer cell lines, AGS and N87, and gene expression was significantly increased following treatment with a demethylating agent, 5-Aza-2'-deoxycytidine. In conclusion, TFF2 expression was markedly decreased in gastric cancer and promoter hypermethylation was found to regulate the downregulation of TFF2. TFF2 has been suggested as a tumor suppressor in gastric carcinogenesis and metastasis.
三叶因子2（TFF2）在胃黏膜中发挥保护作用，可能参与胃癌的进展，但其详细功能及潜在分子机制尚不清楚。本研究采用临床观察与分子方法相结合的方式，探讨TFF2异常表达与胃癌进展之间的相关性。通过逆转录聚合酶链反应（RT-PCR）、定量PCR（qPCR）、蛋白质印迹法及免疫组织化学分析评估TFF2表达。采用基因组亚硫酸氢盐测序法分析TFF2甲基化水平。结果显示，与配对的非癌黏膜相比，胃癌组织中TFF2 mRNA和蛋白表达降低，且降低水平与胃癌的分化和侵袭相关。此外，三个胃癌组织中启动子区域CpG位点的TFF2平均甲基化水平为70.4%，而相关非肿瘤组织中的水平为41.0%。此外，在胃癌细胞系AGS和N87中也发现TFF2启动子高甲基化，用去甲基化剂5-氮杂-2'-脱氧胞苷处理后基因表达显著增加。总之，胃癌中TFF2表达明显降低，且启动子高甲基化可调控TFF2的下调。TFF2被认为是胃癌发生和转移中的一种肿瘤抑制因子。
