CAJ | 학술논문

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因子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VEGFR mRNA、CNTN-1 mRNA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-1 mRNA表达显著增强,而转染了两种shRNA载体的细胞,CNTN-1 mRNA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.
목적 탐토혈관내피생장인자C (VEGF-C)재식관암발전중적작용,병연구VEGF-C여신경계통점부분자-1(CNTN-1)적관계.방법 운용실시정량PCR분석식관암표본화상응적암방조직중VEGF-C/VEGFR적mRNA적표체수평,병구건VEGF-C과표체화기인침묵재체,전염식관암세포주TE-1,검측전염전후CNTN-1적표체차이,병운용염색질면역침정(ChIP)법측정세포전염전후전록인자C/EBP여CNTN-1계동자적상대결합량,이연구VEGF-C시부통과조공CNTN-1기인전록삼여식관암진전.결과 VEGF-C급VEGFR mRNA、CNTN-1 mRNA재종류조직중고표체,차이자지간존재명현상관성.전염VEGF-C과표체재체적TE-1세포중CNTN-1 mRNA표체현저증강,이전염료량충shRNA재체적세포,CNTN-1 mRNA수평균강저(P＜0.01).ChIP측정결과발현재CNTN-1상유C/EBP적결합위점,전염VEGF-C과표체재체후,TE-1세포중C/EBP여CNTN-1계동자적상대결합량현저증고(P＜0.05).결론 식관암조직중VEGF-C급기수체정고표체,여식관암발전상관；VEGF-C가통과영향C/EBP대CNTN-1적전록활성래영향종류세포TE-1적생장화전이.
Objective To investigate the biological significance and mechanism of VEGF-C in esophageal 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-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.Results 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 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).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.