The Expression And Regulation Of MTA2 In Esophageal Cancer Tissues And The Function Mechanism On Esophageal Cancer Cells

Objective:To investigate the expression of metastasis-associated gene 2(MTA2) in esophageal carcinoma and the effects of MTA2 on proliferation, migration and invasion of esophageal cancer cells and to explore the possible molecular mechanism of MTA2 promoting epithelial-mesenchymal transition of esophageal cancer cells.Methods:1 The expression levels of MTA2?Sp1?mi R146A?mi R149?mi R34 A in esophageal carcinoma tissues were detected by q PCR,and the correlation between MTA2 m RNA expression and Sp1?mi R146A?mi R149?mi R34 A expression in esophageal carcinoma tissues or clinicopathological characteristics of patients were also analyzed.2 The protein expression level of MTA2 in normal esophageal epithelial tissues and esophageal carcinoma tissues were detected by western blot and immunohistochemical.3 The proliferation, migration and invasion abilities of esophageal cancer cells with MTA2 low-expression or over-expression were detected by MTS, transwell migration and matrigel invasion chamber assays, respectively.4 The expression levels of EMT related genes of esophageal cancer cells with MTA2 over-expression or low-expression were detected by q PCR.5 The expression levels of EMT related proteins of esophageal cancer cells with MTA2 over-expression or low-expression were detected by western blot.6 The expression levels of EMT related proteins of esophageal cancer cells with MTA2 low-expression were detected by immunofluorescence assay.7 Co-Immunoprecipitation assays detects MTA2 binding to Twist protein8 The expression levels of e IF4 E in normal esophageal epithelial tissues and esophageal carcinoma tissues were detected by q PCR and western blot.9 The migration, invasion abilities and expression levels of EMT related genes as well as proteins of esophageal cancer cells with MTA2 low-expression combining e IF4 E over-expression were detected by transwell assays, q PCR and western blot, respectively.10 The expression levels of Ki-67 and CD31 in nude mice transplanted tumors were detected by immunohistochemical.11 The expression levels of EMT related proteins in nude mice transplanted tumors were detected by western blot.Results:1 q PCR demonstrated that the expression levels of MTA2 in esophageal carcinoma tissues were higher than those in normal esophageal epithelial tissues and adjacent normal esophageal tissues(P<0.05).There were positive correlations between MTA2 m RNA expression and Sp1 m RNA expression in esophageal carcinoma tissues(r=0.407, P<0.05),while there were no correlations between MTA2 and mi R146A?mi R149?mi R34 A expression levels(P>0.05).The expression level of MTA2 was associated with TNM stage and invasion into lymph(P<0.05),not age/year,gender,differentiated degree and tumor size(P>0.05).2 Western blot and immunohistochemical assay demonstrated that the expression level of MTA2 protein in esophageal carcinoma tissues were higher than those in normal esophageal epithelial tissues.3 The MTS assay demonstrated that low-expression of MTA2 could supress the proliferation of KYSE30 and KYSE510(P<0.05),and over-expression of MTA2 had promoting effect on proliferation of KYSE30 and KYSE510(P<0.05).4 The transwell assay showed that low-expression of MTA2 inhibited migration and invasion abilities of KYSE30 and KYSE510(P<0.05),while over-expression of MTA2 promoted migration and invasion abilities of KYSE30 and KYSE510(P<0.05)5 q PCR and western blot demonstrated that low-expression of MTA2 inhibited the expression of N-cadherin,Vimentin,CD24 and MYLK,while promoted the expression of E-cadherin(P<0.05).The over-expression of MTA2 promoted the expression of N-cadherin,Vimentin,CD24 and MYLK,while inhibited the expression of E-cadherin(P<0.05).6 The immunofluorescence assay also showed that low-expression of MTA2 inhibited the expression of N-cadherin and Vimentin,while promoted the expression of E-cadherin.7 Co-Immunoprecipitation assay demonstrated that MTA2 could binding Twist proteins.8 q PCR demonstrated that the expression levels of e IF4 E in esophageal carcinoma tissues were higher than those in normal esophageal epithelial tissues(P<0.05),and the correlation between e IF4 E and MTA2 in esophageal carcinoma tissues was positive( r=0.418,P=0.001).9 The low-expression of MTA2 inhibited the expression level of p-e IF4E(P<0.05).Comparing with MTA2 low-expression,the expression level of E-cadherin in e IF4 E combining MTA2 low-expression was decreased,while the expression level of N-cadherin and Vimentin were increased(P<0.05).The cell migration and invasion abilities were also significantly increased(P<0.05).10 The immunohistochemical assay showed that the expression levels of Ki-67 and CD31 in nude mice transplanted tumors with MTA2 over-expression were higher than those in nude mice transplanted tumors with empty vector.11 Western blot assay demonstrated that the expression levels of N-cadherin and Vimentin in nude mice transplanted tumors with MTA2 over-expression were higher than those in nude mice transplanted tumors with empty vector,while the expression level of E-cadherin was decreased.Conclusions:The expression level of MTA2 in esophageal carcinoma tissues is significantly increased,and it may be related to the Sp1 higher expression. MTA2 could promote the proliferation of esophageal cancer cells in vitro and in vivo.MTA2 also could promote the migration and invasion abilities of esophageal cancer cells in vitro,this effect may be related to promoting the expression of p-e IF4 E.