VEGF-C facilitates development of esophageal squamous cancer via regulating expression of CNTN-1 / 中华消化内镜杂志

ABSTRACT

ObjectiveTo investigate the biological significance and mechanism of VEGF-C in esophageal tumor development,and correlation of CNTN-1 level with VEGF-C.MethodsThe expression of VEGF-C and its receptors in esophageal squamous cancer cell (ESCC) and in corresponding noncancerous esophageal tissue specimens were detected by real-tithe PCR.Esophageal squamous cancer cell line TE-1 was transinfected by VEGF-C overexpression and gene silencing vectors,respectively,and the relative amount of C/EBP bound to CNTN-1 promoter was determined by quantitative ChIP,to explore the possibility that VEGF-C was involved in development of esophageal cancer through mediating transcription of CNTN-1.ResultsThe mRNA levels of VEGF-C was significantly higher in ESCC than in normal esophageal tissues.VEGF-C expression was significantly increased in VEGF-C-overexpressing TE-1 cells compared to untransfected cells (mock).Cells transfected with either of the VEGF-C targeting shRNA vectors,shRNA-1 and shRNA-2,showed reduced VEGF-C transcripts (P ＜ 0.01 ).Expression levels of VEGF-C and CNTN-1 mRNA correlated significantly with each other.The binding site of C/EBP in CNTN-1 was detected by ChIP,and the relative amount of C/EBP binding to CNTN-1 promoter was significantly increased in TE-1 after transfecting by VEGF-C overexpression vector ( P ＜ 0.05).ConclusionVEGF-C and its receptor are highly expressed in esophageal cancer tissues,which may be associated with ESCC carcinogenesis and development.VEGF-C may influence on growth and migration in TE-1 cells through CNTN-1.