Promoter hypermethylation and downregulation of trefoil factor 2 in human gastric cancer.
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.
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.
Ping
P
Jiang
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.
Guoyu
G
Yu
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.
Yong
Y
Zhang
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.
Yang
Y
Xiang
Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China.
Zhu
Z
Zhu
Department of Biochemistry, Kunming Medical University, Kunming, Yunnan 650500, P.R. China.
Weiyang
W
Feng
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.
Wenhui
W
Lee
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.
Yun
Y
Zhang
downregulation; gastric cancer; promoter hypermethylation; trefoil factor 2