Overexpression of ZEB1 associated with metastasis and invasion in patients with gastric carcinoma

被引:57
作者
Jia, Baoqing [1 ]
Liu, Hongyi [1 ]
Kong, Qinglong [1 ]
Li, Bing [1 ]
机构
[1] Chinese Peoples Liberat Army, Dept Surg Oncol, Gen Hosp, Beijing 100853, Peoples R China
关键词
Gastric carcinoma; Metastasis; ZEB1; RNAi; E-CADHERIN; TRANSCRIPTIONAL REPRESSOR; PROSTATE-CANCER; DOWN-REGULATION; EXPRESSION; PLASTICITY; MANAGEMENT; DELTA-EF1; GENE; EMT;
D O I
10.1007/s11010-012-1299-6
中图分类号
Q2 [细胞生物学];
学科分类号
071013 [干细胞生物学];
摘要
The aim of this study was to investigate the expression of ZEB1 in gastric carcinoma, its correlation with the clinicopathology of gastric carcinoma, and the role of ZEB1 in invasion and metastasis in gastric carcinoma. ZEB1 expression was analyzed by immunohistochemistry and Western blot in 45 gastric carcinoma tissue samples that contained the adjacent gastric mucosa. The correlation between ZEB1 expression, the occurrence and development of gastric cancer, and clinical pathology was investigated. ZEB1 expression in the human gastric carcinoma cell line AGS was downregulated by RNA interference, and changes in ZEB1 expression corresponded with changes in the invasive and metastatic ability of AGS cells. Immunohistochemistry revealed that ZEB1 protein expression in gastric carcinoma tissues was significantly higher than in normal gastric mucosa tissues (p < 0.001). A lower degree of differentiation of gastric cancer (p = 0.009), a higher TNM (tumor, node, and metastasis) stage (p = 0.010), and a larger scope of invasion were correlated with higher expression of ZEB1 (p = 0.041, 0.002). However, the expression of ZEB1 in gastric carcinoma tissue was independent of gender, age, and tumor size (p > 0.05). Western blot results also showed that ZEB1 protein expression was significantly higher in gastric carcinoma tissue than in the adjacent normal gastric mucosa tissue (p = 0.008). A lower degree of differentiation of the gastric carcinoma correlated with a higher TNM stage, and a larger scope of invasion correlated with increased ZEB1 expression (p = 0.023). Transfection of ZEB1 siRNA in AGS cells significantly decreased the expression level of ZEB1 protein (p = 0.035). Furthermore, the number of cells that could pass through the Transwell chamber was significantly lower in the transfected group than in the non-transfected control group (p = 0.039), indicating that the suppression of ZEB1 expression could significantly reduce the invasive and metastatic ability of AGS cells (p = 0.005). Concluding, in gastric carcinoma tissue, overexpression of ZEB1 may be related to the occurrence and development as well as invasion and metastasis of gastric carcinoma.
引用
收藏
页码:223 / 229
页数:7
相关论文
共 38 条
[1]
Bae KM, 2011, AM J CANCER RES, V1, P71
[2]
RETRACTED: Notch-1 induces epithelial-mesenchymal transition consistent with cancer stem cell phenotype in pancreatic cancer cells (Retracted article. See vol. 423, pg. 153, 2018) [J].
Bao, Bin ;
Wang, Zhiwei ;
Ali, Shadan ;
Kong, Dejuan ;
Li, Yiwei ;
Ahmad, Aamir ;
Banerjee, Sanjeev ;
Azmi, Asfar S. ;
Miele, Lucio ;
Sarkar, Fazlul H. .
CANCER LETTERS, 2011, 307 (01) :26-36
[3]
Fibre-based post systems: a review [J].
Bateman, G ;
Ricketts, DNJ ;
Saunders, WP .
BRITISH DENTAL JOURNAL, 2003, 195 (01) :43-48
[4]
Cyclooxygenase-2-dependent regulation of E-cadherin:: Prostaglandin E2 induces transcriptional repressors ZEB1 and snail in non-small cell lung cancer [J].
Dohadwala, Mariam ;
Yang, Seok-Chul ;
Luo, Jie ;
Sharma, Sherven ;
Batra, Raj K. ;
Huang, Min ;
Lin, Ying ;
Goodglick, Lee ;
Krysan, Kostyantyn ;
Fishbein, Michael C. ;
Hong, Longsheng ;
Lai, Chi ;
Cameron, Robert B. ;
Gemmill, Robert M. ;
Drabkin, Harry A. ;
Dubinett, Steven M. .
CANCER RESEARCH, 2006, 66 (10) :5338-5345
[5]
DeltaEF1 is a transcriptional repressor of E-cadherin and regulates epithelial plasticity in breast cancer cells [J].
Eger, A ;
Aigner, K ;
Sonderegger, S ;
Dampier, B ;
Oehler, S ;
Schreiber, M ;
Berx, G ;
Cano, A ;
Beug, H ;
Foisner, R .
ONCOGENE, 2005, 24 (14) :2375-2385
[6]
Correlation of E-cadherin, VEGF, COX-2 expression to prognostic parameters in papillary thyroid carcinoma [J].
Erdem, Havva ;
Gundogdu, Cemal ;
Sipal, Sare .
EXPERIMENTAL AND MOLECULAR PATHOLOGY, 2011, 90 (03) :312-317
[7]
The transcriptional repressor ZEB regulates p73 expression at the crossroad between proliferation and differentiation [J].
Fontemaggi, G ;
Gurtner, A ;
Strano, S ;
Higashi, Y ;
Sacchi, A ;
Piaggio, G ;
Blandino, G .
MOLECULAR AND CELLULAR BIOLOGY, 2001, 21 (24) :8461-8470
[8]
Down-regulation of TCF8 is involved in the leukemogenesis of adult T-cell leukemia/lymphoma [J].
Hidaka, Tomonori ;
Nakahata, Shingo ;
Hatakeyama, Kinta ;
Hamasaki, Makoto ;
Yamashita, Kiyoshi ;
Kohno, Takashi ;
Arai, Yasuhito ;
Taki, Tomohiko ;
Nishida, Kazuhiro ;
Okayama, Akihiko ;
Asada, Yujiro ;
Yamaguchi, Ryoji ;
Tsubouchi, Hirohito ;
Yokota, Jun ;
Taniwaki, Masafumi ;
Higashi, Yujiro ;
Morishita, Kazuhiro .
BLOOD, 2008, 112 (02) :383-393
[9]
FDG PET imaging in the staging and management of gastric cancer [J].
Hopkins, Shane ;
Yang, Gary Y. .
JOURNAL OF GASTROINTESTINAL ONCOLOGY, 2011, 2 (01) :39-44
[10]
Jensen Kendal, 2012, Transl Gastrointest Cancer, V1, P81