中文摘要：

目的探讨血管内皮生长因子C（VEGF—C）在食管癌发展中的作用，并研究VEGF—C与神经系统黏附分子-1（CNTN-1）的关系。方法运用实时定量PCR分析食管癌标本和相应的癌旁组织中VEGF—C／VEGFR的mRNA的表达水平，并构建VEGF—C过表达和基因沉默载体，转染食管癌细胞株TE-1，检测转染前后CNTN-1的表达差异，并运用染色质免疫沉淀（CHIP）法测定细胞转染前后转录凶子C／EBP与CNTN-1启动子的相对结合量，以研究VEGF—C是否通过调控CNTN-1基因转录参与食管癌进展。结果VEGF—C及VEGFRmRNA、CNTN-1mRNA在肿瘤组织中高表达，且二者之间存在明显相关性。转染VEGF—C过表达载体的TE-1细胞中CNTN-1mRNA表达显著增强，而转染了两种shRNA载体的细胞，CNTN-1mRNA水平均降低（P〈0．01）。ChIP测定结果发现在CNTN-1上有C／EBP的结合位点，转染VEGF—C过表达载体后，TE-1细胞中C／EBP与CNTN-1启动子的相对结合量显著增高（P〈0．05）。结论食管癌组织中VEGF—C及其受体呈高表达，与食管癌发展相关；VEGF—C可通过影响C／EBP对CNTN-1的转录活性来影响肿瘤细胞TE-1的生长和转移。

英文摘要：

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.