Gene Silencing of β-catenin by RNAi Inhibits Proliferation of Human Esophageal Cancer Cells by Inducing G0/G1 Cell Cycle Arrest

被引:10
作者
Wang, Jin-Sheng [1 ]
Ji, Ai-Fang [1 ]
Wan, Hong-Jun [2 ]
Lu, Ya-Li [3 ]
Yang, Jian-Zhou [1 ]
Ma, Li-Li [1 ]
Wang, Yong-Jin [1 ]
Wei, Wu [1 ]
机构
[1] Changzhi Med Univ, Peace Hosp, Cent Lab, Changzhi, Peoples R China
[2] Shanxi Med Univ, Jinci Coll, Taiyuan, Peoples R China
[3] Jiamusi Univ, Basic Sch Med, Dept Pathol & Pathophysiol, Jiamusi, Peoples R China
关键词
beta-catenin; esophageal carcinoma; cell cycle; cyclin D1; extracellular signal; regulated kinase1/2; D1; GENES; C-MYC; EXPRESSION; CARCINOMA; GROWTH;
D O I
10.7314/APJCP.2012.13.6.2527
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Objectives: The aim of the present study was to explore mechanisms underlying the effects of down-regulating beta-catenin expression on esophageal carcinoma (EC) cells. Methods: Cell cycle distribution and apoptosis were determined using flow cytometry and annexin V apoptosis assay, respectively. Transmission electron microscopy (TEM) was used to examine changes in ultrastructure, while expression of cyclin D1 protein and mRNA was detected by western blot and real-time PCR. Proliferating cell nuclear antigen (PCNA) and extracellular signal-regulated kinase (ERK) 1/2 were evaluated by Western blot analysis. PCNA labeling index (LI) was determined by immunocytochemistry. Results: Compared with pGen-3-con transfected and Eca-109 cells, the percentage of G0/G1-phase pGen-3-CTNNB1 transfected cells was obviously increased (P<0.05), with no significant difference among the three groups with regard to apoptosis (P>0.05). pGen-3-CTNNB1 transfected cells exhibited obvious decrease in cyclin D1 mRNA and protein expression (P<0.05) and the ultrastructure of Eca-109 cells underwent a significant change after being transfected with pGen-3-CTNNB1, suggesting that down-regulating beta-catenin expression can promote the differentiation and maturation. The expression of PCNA and the ERKI/2 phosphorylation state were also down-regulated in pGen-3-CTNNB1 transfected cells (P<0.05). At the same time, the PCNA labeling index was decreased accordingly (P<0.05). Conclusion: Inhibition of EC Eca-109 cellproliferation by down-regulating beta-catenin expression could improve cell ultrastructure by mediating blockade in G0/G1 through inhibiting cyclin D1, PCNA and the MAPK pathway (p-ERK1/2).
引用
收藏
页码:2527 / 2532
页数:6
相关论文
共 26 条
[1]   Linking cyclins to transcriptional control [J].
Coqueret, O .
GENE, 2002, 299 (1-2) :35-55
[2]   β-Catenin expression pattern in primary oesophageal squamous cell carcinoma.: Relationship with clinicopathologic features and clinical outcome [J].
de Castro, J ;
Gamallo, C ;
Palacios, J ;
Moreno-Bueno, G ;
Rodríguez, N ;
González-Barón, JFM .
VIRCHOWS ARCHIV-AN INTERNATIONAL JOURNAL OF PATHOLOGY, 2000, 437 (06) :599-604
[3]  
Deng Yong-Jun, 2007, Ai Zheng, V26, P693
[4]   Expression level of beta-catenin is associated with prognosis of esophageal carcinoma [J].
Ji, Lv ;
Cao, Xiu-Feng ;
Wang, He-Ming ;
Li, Yi-Sheng ;
Zhu, Bin ;
Xiao, Lian ;
Wang, Dan .
WORLD JOURNAL OF GASTROENTEROLOGY, 2007, 13 (18) :2622-2625
[5]  
Kimura Y, 1999, INT J CANCER, V84, P174, DOI 10.1002/(SICI)1097-0215(19990420)84:2<174::AID-IJC14>3.3.CO
[6]  
2-5
[7]   The complexity of mitogen-activated protein kinases (MAPKs) made simple [J].
Krishna, M. ;
Narang, H. .
CELLULAR AND MOLECULAR LIFE SCIENCES, 2008, 65 (22) :3525-3544
[8]   Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method [J].
Livak, KJ ;
Schmittgen, TD .
METHODS, 2001, 25 (04) :402-408
[9]   The ERK1/2 mitogen-activated protein kinase pathway as a master regulator of the G1- to S-phase transition [J].
Meloche, S. ;
Pouyssegur, J. .
ONCOGENE, 2007, 26 (22) :3227-3239
[10]  
Nunez R, 2001, Curr Issues Mol Biol, V3, P67