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http://dx.doi.org/10.7314/APJCP.2012.13.6.2527

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

Wang, Jin-Sheng (Central Laboratory, Peace Hospital Affiliated to Changzhi Medical University)
Ji, Ai-Fang (Central Laboratory, Peace Hospital Affiliated to Changzhi Medical University)
Wan, Hong-Jun (Jinci College, Shanxi Medical University)
Lu, Ya-Li (Department of Pathology and Pathophysiology, Basic School of Medicine, Jiamusi University)
Yang, Jian-Zhou (Central Laboratory, Peace Hospital Affiliated to Changzhi Medical University)
Ma, Li-Li (Central Laboratory, Peace Hospital Affiliated to Changzhi Medical University)
Wang, Yong-Jin (Central Laboratory, Peace Hospital Affiliated to Changzhi Medical University)
Wei, Wu (Central Laboratory, Peace Hospital Affiliated to Changzhi Medical University)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.13, no.6, 2012 , pp. 2527-2532 More about this Journal
Abstract
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).
Keywords
${\beta}$-catenin; esophageal carcinoma; cell cycle; cyclin D1; extracellular signal; regulated kinase1/2;
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