Cunniffe C, Ryan F, Lambkin H, Brankin B
School of Biological Sciences, Dublin Institute of Technology, Kevin Street, Dublin 8, Ireland.
Br J Biomed Sci. 2012;69(4):147-53.
Adherens junctions (AD and tight junctions (TJ) play a key role in maintaining the apical-basolateral polarity and cohesive structure of epithelial cells. These epithelial junctions are maintained by the interaction of several key proteins including E-cadherin, claudins, occludin and zona-occludens. The zinc finger protein, Snail, has previously been identified as a possible regulator of several of these AJ and TJ proteins. Expression levels of ZO-1, occludin, claudins, E-cadherin, human Scribble protein and Snail were determined in HeLa and CaSki cervical carcinoma cell lines by imuunohistochemistry (IHC) and Western blotting. In tandem, tissue microarrays were utilised in the IHC-based detection of E-cadherin in 26 cases of non-cancerous cervical tissue, 15 cases of cervical intraepithelial neoplasia 1 (CIN1), 11 cases of CIN2, 12 cases of CIN3, 50 cases of squamous cell carcinoma and two cases of adenocarcinoma. This study found aberrant E-cadherin expression in CIN lesions and cases of squamous cell carcinoma compared to normal epithelium. HeLa cells were E-cadherin-negative while CaSki cells were positive, with HeLa cells showing a high level of Snail expression. Occludin and ZO-1 expression was detected in both cell lines. No expression was observed for claudin 1 or claudin 5 tight junction proteins in HeLa cells or CaSki cells. Loss of expression of claudin 1, claudin 5 and E-cadherin, with concomitant increase in Snail may be associated with loss of epithelial cell polarity and alterations in intercellular adhesion.
黏着连接(AD)和紧密连接(TJ)在维持上皮细胞的顶-基极性和黏附结构中起关键作用。这些上皮连接由包括E-钙黏蛋白、闭合蛋白、闭锁蛋白和闭合小带蛋白等几种关键蛋白的相互作用维持。锌指蛋白Snail先前已被确定为这些黏着连接和紧密连接蛋白中几种蛋白的可能调节因子。通过免疫组织化学(IHC)和蛋白质印迹法测定了HeLa和CaSki宫颈癌细胞系中ZO-1、闭锁蛋白、闭合蛋白、E-钙黏蛋白、人Scribble蛋白和Snail的表达水平。同时,利用组织微阵列通过免疫组织化学检测26例非癌性宫颈组织、15例宫颈上皮内瘤变1级(CIN1)、11例CIN2、12例CIN3、50例鳞状细胞癌和2例腺癌中E-钙黏蛋白的表达。本研究发现,与正常上皮相比,CIN病变和鳞状细胞癌病例中E-钙黏蛋白表达异常。HeLa细胞E-钙黏蛋白阴性,而CaSki细胞阳性,HeLa细胞显示出高水平的Snail表达。在两种细胞系中均检测到闭锁蛋白和ZO-1的表达。在HeLa细胞或CaSki细胞中未观察到闭合蛋白1或闭合蛋白5紧密连接蛋白的表达。闭合蛋白1、闭合蛋白5和E-钙黏蛋白表达缺失,同时Snail增加,可能与上皮细胞极性丧失和细胞间黏附改变有关。