VEGF-C facilitates development of esophageal squamous cancer via regulating expression of CNTN-1

Abstract

Objective To investigate the biological significance and mechanism of VEGF-C in e- sophageal tumor development, and correlation of CNTN-1 level with VEGF-C. Methods The expression of VEGF-C and its receptors in esophageal squamous cancer cell （ESCC） and in corresponding noncancerous esophageal tissue specimens were detected by real-time 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. Re- suits The 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 untrans- fected 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 mR- NA 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 ）. Conclusion VEGF-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. Key words: Esophageal tumor; VEGF-C; CNTN-1