Skoudy A, Gomez S, Fabre M, Garcia de Herreros A
Unitat de Biologia Cel.lular i Molecular, Institut Municipal d'Investigació Mèdica, Universitat Autònoma de Barcelona, Spain.
Int J Cancer. 1996 Sep 27;68(1):14-20. doi: 10.1002/(SICI)1097-0215(19960927)68:1<14::AID-IJC3>3.0.CO;2-#.
Recent data suggest that p120-catenin plays a role in the regulation of functionality of E-cadherin, a protein essential for the establishment and maintenance of cell-cell contacts. Since dysfunction of intercellular adhesiveness is an alteration frequently observed in colon cancer we have studied the expression and distribution of p120-catenin in human colorectal tumors. In normal colon, p120-catenin was observed in the crypt and surface epithelium; the cells showed reactivity both in the membrane and in the cytosol. Thirteen primary tumors were examined for p120-catenin expression: they were graded as uniformly positives (+) (4); heterogeneous (+/-) (6), with a diminished expression, detected mainly in the cytosol; and negatives (-) (3). Although the number of tumors was low, the reduction in p120-catenin correlated with a larger size of the tumors (p = 0.038). Association of p120-catenin to the cytoskeleton was also determined in 5 tumors by detergent extraction and Western blot; this analysis shows that lack of reactivity in the membrane was accompanied by absence of p120-catenin in the cytoskeleton-associated fraction. Analysis of E-cadherin was performed in order to compare the distribution of this protein and p120-catenin. Although no complete correlation was found between the expression of both proteins (p = 0.077), our results showed that alterations in the level or distribution of p120-catenin were accompanied by lack of E-cadherin reactivity in the membrane, whereas absence of p120-catenin in the cytoskeleton fraction was associated with important decreases in the amount of E-cadherin in this same fraction. These results show that alterations in p120-catenin levels are a common event in colorectal tumors, and suggest that the distribution of this protein and E-cadherin is coordinately regulated.
近期数据表明，p120连环蛋白在E-钙黏蛋白功能调节中发挥作用，E-钙黏蛋白是一种对细胞间接触的建立和维持至关重要的蛋白质。由于细胞间黏附功能障碍是结肠癌中常见的一种改变，我们研究了p120连环蛋白在人类结直肠肿瘤中的表达和分布。在正常结肠中，p120连环蛋白见于隐窝和表面上皮；细胞在细胞膜和细胞质中均显示出反应性。对13例原发性肿瘤进行了p120连环蛋白表达检测：它们被分级为均匀阳性（+）（4例）；异质性（+/-）（6例），表达减少，主要在细胞质中检测到；阴性（-）（3例）。尽管肿瘤数量较少，但p120连环蛋白的减少与肿瘤较大尺寸相关（p = 0.038）。还通过去污剂提取和蛋白质印迹法在5例肿瘤中测定了p120连环蛋白与细胞骨架的结合；该分析表明，细胞膜中缺乏反应性伴随着细胞骨架相关组分中p120连环蛋白的缺失。进行了E-钙黏蛋白分析以比较该蛋白和p120连环蛋白的分布。尽管两种蛋白的表达之间未发现完全相关性（p = 0.077），但我们的结果表明，p120连环蛋白水平或分布的改变伴随着细胞膜中E-钙黏蛋白反应性的缺乏，而细胞骨架组分中p120连环蛋白的缺失与该相同组分中E-钙黏蛋白量的显著减少相关。这些结果表明，p120连环蛋白水平的改变在结直肠肿瘤中是常见事件，并表明该蛋白和E-钙黏蛋白的分布受到协调调节。
