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

被引：46
|
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.
引用
收藏
页码：1526 / 1534
页数：9
相关论文
共 50 条
  • [1] Aberrant Methylation of Promoter Region of SPINT2/HAI-2 Gene: An Epigenetic Mechanism in Hepatitis C Virus-Induced Hepatocarcinogenesis
    Ramadan, Ragaa A.
    Zaki, Moyassar A.
    Awad, Ahmed M.
    El-Ghalid, Lamiaa A.
    GENETIC TESTING AND MOLECULAR BIOMARKERS, 2015, 19 (07) : 399 - 404
  • [2] SPINT2 (HAI-2) missense variants identified in congenital sodium diarrhea/tufting enteropathy affect the ability of HAI-2 to inhibit prostasin but not matriptase
    Holt-Danborg, Lasse
    Vodopiutz, Julia
    Nonboe, Annika W.
    De Laffolie, Jan
    Skovbjerg, Signe
    Wolters, Victorien M.
    Mueller, Thomas
    Hetzer, Benjamin
    Querfurt, Alexander
    Zimmer, Klaus-Peter
    Jensen, Jan K.
    Entenmann, Andreas
    Heinz-Erian, Peter
    Vogel, Lotte K.
    Janecke, Andreas R.
    HUMAN MOLECULAR GENETICS, 2019, 28 (05) : 828 - 841
  • [3] STYK1 promotes tumor growth and metastasis by reducing SPINT2/HAI-2 expression in non-small cell lung cancer
    Zhiqiang Ma
    Dong Liu
    Weimiao Li
    Shouyin Di
    Zhipei Zhang
    Jiao Zhang
    Liqun Xu
    Kai Guo
    Yifang Zhu
    Jing Han
    Xiaofei Li
    Xiaolong Yan
    Cell Death & Disease, 10
  • [4] STYK1 promotes tumor growth and metastasis by reducing SPINT2/HAI-2 expression in non-small cell lung cancer
    Ma, Zhiqiang
    Liu, Dong
    Li, Weimiao
    Di, Shouyin
    Zhang, Zhipei
    Zhang, Jiao
    Xu, Liqun
    Guo, Kai
    Zhu, Yifang
    Han, Jing
    Li, Xiaofei
    Yan, Xiaolong
    CELL DEATH & DISEASE, 2019, 10 (6)
  • [5] Tumor suppressor activity and epigenetic inactivation of hepatocyte growth factor activator inhibitor type 2/SPINT2 in papillary and clear cell renal cell carcinoma
    Morris, MR
    Gentle, D
    Abdulrahman, M
    Maina, EN
    Gupta, K
    Banks, RE
    Wiesener, MS
    Kishida, T
    Yao, M
    Teh, B
    Latif, F
    Maher, ER
    CANCER RESEARCH, 2005, 65 (11) : 4598 - 4606
  • [6] Epigenetic inactivation of SPINT2 is associated with tumor suppressive function in esophageal squamous cell carcinoma
    Yue, Dongli
    Fan, Qingxia
    Chen, Xinfeng
    Li, Feng
    Wang, Liping
    Huang, Lan
    Dong, Wenjie
    Chen, Xiaoqi
    Zhang, Zhen
    Liu, Jinyan
    Wang, Fei
    Wang, Meng
    Zhang, Bin
    Zhang, Yi
    EXPERIMENTAL CELL RESEARCH, 2014, 322 (01) : 149 - 158
  • [7] Epigenetic downregulation of SPINT2 in aneuploidy.
    Zhang, H.
    Li, H.
    Ganem, N.
    Pellman, D.
    MOLECULAR BIOLOGY OF THE CELL, 2014, 25
  • [8] An Epigenetic Genome-Wide Screen Identifies SPINT2 as a Novel Tumor Suppressor Gene in Pediatric Medulloblastoma
    Kongkham, Paul N.
    Northcott, Paul A.
    Ra, Young Shin
    Nakahara, Yukiko
    Mainprize, Todd G.
    Croul, Sidney E.
    Smith, Christian A.
    Taylor, Michael D.
    Rutka, James T.
    CANCER RESEARCH, 2008, 68 (23) : 9945 - 9953
  • [9] Epigenetic silencing of SPINT2 enhances tumorigenicity of glioblastoma
    Fukushima, Tsuyoshi
    Kawaguchi, Makiko
    Yamamoto, Koji
    Tanaka, Hiroyuki
    Kataoka, Hiroaki
    CANCER SCIENCE, 2018, 109 : 1128 - 1128
  • [10] Methylation of HAI-2/SPINT2 in Bone Marrow Mesenchymal Stromal Cells of MDS and AML Patients Affects Hematopoietic Stem Cell Survival and Adhesion
    Roversi, Fernanda Marconi
    Cury, Nathalia Moreno
    Lopes, Matheus Rodrigues
    Pericole, Fernando Vieira
    Alvarez Prax, Marisa Claudia
    Ferro, Karla Priscila
    Favaro, Patricia
    Yunes, Jose Andres
    Olalla Saad, Sara T.
    BLOOD, 2015, 126 (23)
12345