摘要
背景与目的:上皮性钙粘附蛋白(E-cadherin)和神经性钙粘附蛋白(N-cadherin)在细胞的迁徙和肿瘤浸润转移方面有着重要的作用。许多研究表明,E-cadherin是作为一种抑癌基因发挥作用的,与之相反,N-cadherin在促进肿瘤的浸润转移方面具有重要作用。本研究探讨N-cadherin在食管鳞癌组织中的表达及其临床病理意义,以及RNA干扰(RNAi)沉默N-cadherin基因表达对人食管癌细胞系EC9706细胞体外侵袭能力的影响。方法:采用免疫组织化学PV法检测62例食管鳞癌组织、31例癌旁不典型增生组织及62例正常食管粘膜组织中E-cadherin、N-cadherin的蛋白表达。通过逆转录病毒介导的RNAi技术沉默EC9706细胞中N-cadherin的表达,观察该细胞体外侵袭能力的变化。结果:正常食管粘膜组织、癌旁不典型增生组织及食管鳞癌组织中E-cadherin的阳性率依次降低,分别为95.2%、71.0%、40.3%;N-cadherin的阳性率依次升高,分别为29.0%、61.3%、75.8%。E-cadherin的阴性率及N-cadherin的阳性率与食管鳞癌的浸润深度、分化程度及淋巴结转移密切相关(P<0.05),二者在食管鳞癌组织中的表达呈负相关关系(r=-0.534,P<0.05)。稳定干扰后的EC9706细胞中N-cadherin的mRNA和蛋白表达水平均下调。Transwell小室体外侵袭实验结果显示,正常对照组的穿膜细胞数为123.4±8.2,而干扰载体组的穿膜细胞数则为49.6±6.8(P<0.05)。结论:食管鳞癌组织中E-cadherin的低表达和N-cadherin的高表达与食管鳞癌的发生、浸润及转移密切相关;RNAi沉默N-cadherin基因表达可以使EC9706细胞的体外侵袭能力降低。
Background and Objective: E- and N-cadherin are calciumdependent cell adhesion molecules that modulate cell migration and tumor invasion. It has been suggested that, unlike E-cadherin, N-cadherin may promote invasion and metastasis of carcinoma. This study was to explore the correlation of E-cadherin and N-cadherin expression to clinicopathologic features of esophageal squamous cell carcinoma (ESCC), and to investigate the effect of silencing N-cadherin expression by RNA interference (RNAi) on the invasiveness of EC9706 cells. Methods. PV immunohistochemistry was used to detect the expression of E-eadherin and N-cadherin in 62 specimens of normal esophageal epithelium, 31 specimens of adjacent atypical hyperplasia epithelium and 62 specimens of ESCC. N-cadherin siRNA was transfected into EC9706 cells, and the effect of RNAi was assessed by RT-PCR and Western blot. The invasiveness of EC9706 cells was determined by Transwell chamber assay. Results: The positive rates of E-cadherin and N-cadherin were 95.2% and 29.0% in normal esophageal epithelium, 71.0% and 61.3% in adjacent atypical hyperplasia epithelium, 40.3% and 75.8% in ESCC. The negativity of E-cadherin and positivity of N-cadherin were correlated to invasion, differentiation, and lymph node metastasis of ESCC (P〈0.05). E-cadherin expression was negatively correlated to N-cadherin expression in ESCC (r=-0.534, P〈0.05). N-cadherin RNAi significantly inhibited N-cadherin expression in EC9706 cells, and decreased the number of EC9706 cells that invaded through the basement membrane from (123.4± 8.2) to (49.6±6.8) (P〈0.05). Conclusion: Down-regulation of E-cadherin and up-regulation of N-cadherin may be involved in the genesis of ESCC. Silencing N-cadherin using RNA interference could impair the invasiveness of EC9706 cells in vitro.
出处
《癌症》
SCIE
CAS
CSCD
北大核心
2009年第1期11-18,共8页
Chinese Journal of Cancer
基金
河南省科技厅科技攻关项目(072102310054)~~