Epigenetic inactivation and tumor suppressor activity of HAI-2/SPINT2 in gastric cancer

被引：47
作者：
Dong, Wenjie
Chen, Xiaobing [2 ]
Xie, Jing [3 ]
Sun, Pinghu
Wu, Yunlin [1 ]
机构：
[1] Shanghai Jiao Tong Univ, Sch Med, Rui Jin Hosp, Dept Gastroenterol, Shanghai 200025, Peoples R China
[2] Henan Tumor Hosp, Dept Med Oncol, Zhengzhou, Peoples R China
[3] Shanghai Jiao Tong Univ, Dept Pathol, Rui Jin Hosp, Shanghai 200025, Peoples R China
来源：
INTERNATIONAL JOURNAL OF CANCER | 2010年 / 127卷 / 07期
关键词：
gastric cancer; methylation; HAI-2/SPINT2; HEPATOCYTE GROWTH-FACTOR; FACTOR ACTIVATOR INHIBITOR; RENAL-CELL CARCINOMA; HUMAN BREAST-CANCER; C-MET; OVARIAN-CANCER; PROTEASE INHIBITOR; BIKUNIN HAI-2/PB; MOUSE MODEL; EXPRESSION;
D O I：
10.1002/ijc.25161
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Hepatocyte growth factor (HGF) activator inhibitor type 2 (HAI-2/SPINT2) encodes Kunitz-type protease inhibitor that regulates HGF activity. Inspection of the human HAI-2/SPINT2 locus uncovered a large and dense CpG island within the 5' region of this gene. Analysis of cultured human gastric tumor lines indicated that HAI-2/SPINT2 expression is either undetectable or in low abundance in several lines; however, enhanced gene expression was measured in cells cultured on the DNA demethylating agent 5-aza-2'-deoxycytidine. Bisulfite DNA sequencing confirmed the densely methylated HAI-2/SPINT2 promoter region. Forced expression of HAI-2/SPINT2 induced cell apoptosis, suppressed anchorage independent growth in vitro and tumor growth in vivo. We investigated HAI-2/SPINT2 aberrant methylation in patients with gastric cancer. The HAI-2/SPINT2 methylation was found preferentially in cancerous tissues (30 of 40, 75%) compared with nontumor tissues (no methylation was detected), indicating that this aberrant characteristic is common in gastric malignancies. In conclusion, epigenetic inactivation of HAI-2/SPINT2 is a common event contributing to gastric carcinogenesis and may be a potential biomarker for gastric cancer.
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页码：1526 / 1534
页数：9
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