Khare L, Sabourin C L, De Young B R, Jamasbi R J, Stoner G D
Department of Pathology, School of Public Health, The Ohio State University, Columbus, OH 43210, USA.
Int J Oncol. 1999 Jan;14(1):33-40.
An alteration in the localization of E-cadherin and its associated proteins has been observed in many epithelial neoplasms. No data exist, however, for the expression of these proteins in an animal model system for esophageal cancer or in cultured rat esophageal epithelial cell lines. The present study investigated the localization of E-cadherin and its associated protein, alpha-catenin, in rat esophageal epithelial cell lines of differing tumorigenic potential; in tumors induced after transplantation of these cell lines into syngeneic hosts; and, in esophageal tumors induced in rats by the carcinogen, N-nitrosomethylbenzylamine (NMBA). Immunofluorescent staining of the cultured cell lines revealed staining for both E-cadherin and alpha-catenin at cell-cell boundaries. Western blot analysis confirmed the membrane-bound localization of E-cadherin and alpha-catenin in the cells. However, tumors induced by these cell lines in syngeneic rats showed reduction in the expression of both E-cadherin and á-catenin in the plasma membrane of invasive epithelial cells. Immunohistochemical analysis of NMBA-induced esophageal neoplasms in rats revealed E-cadherin and alpha-catenin to be abnormally expressed in poorly differentiated tumors when compared to well differentiated tumors. These results suggest that the microenvironment may have an important role in regulating the expression of these adhesion molecules in rat esophageal epithelial cells, and that alteration in the cellular localization of E-cadherin and alpha-catenin may be indicative of tumor progression in NMBA-induced rat esophageal cancer.
在许多上皮性肿瘤中都观察到了E-钙黏蛋白及其相关蛋白定位的改变。然而,尚无关于这些蛋白在食管癌动物模型系统或培养的大鼠食管上皮细胞系中表达情况的数据。本研究调查了E-钙黏蛋白及其相关蛋白α-连环蛋白在具有不同致瘤潜能的大鼠食管上皮细胞系中的定位;将这些细胞系移植到同基因宿主后诱导产生的肿瘤中的定位;以及致癌物N-亚硝基甲基苄胺(NMBA)诱导的大鼠食管肿瘤中的定位。对培养的细胞系进行免疫荧光染色显示,E-钙黏蛋白和α-连环蛋白在细胞间边界处均有染色。蛋白质印迹分析证实了E-钙黏蛋白和α-连环蛋白在细胞中的膜结合定位。然而,这些细胞系在同基因大鼠中诱导产生的肿瘤显示,侵袭性上皮细胞膜中E-钙黏蛋白和α-连环蛋白的表达均降低。对NMBA诱导的大鼠食管肿瘤进行免疫组织化学分析发现,与高分化肿瘤相比,低分化肿瘤中E-钙黏蛋白和α-连环蛋白表达异常。这些结果表明,微环境可能在调节大鼠食管上皮细胞中这些黏附分子的表达方面发挥重要作用,并且E-钙黏蛋白和α-连环蛋白细胞定位的改变可能表明NMBA诱导的大鼠食管癌的肿瘤进展。