异常的P-钙黏蛋白表达是结肠增生和发育异常转变过程中的早期事件。
Aberrant P-cadherin expression is an early event in hyperplastic and dysplastic transformation in the colon.
作者信息
Hardy R G, Tselepis C, Hoyland J, Wallis Y, Pretlow T P, Talbot I, Sanders D S A, Matthews G, Morton D, Jankowski J A Z
机构信息
Department of Surgery, University of Birmingham, Birmingham, UK.
出版信息
Gut. 2002 Apr;50(4):513-9. doi: 10.1136/gut.50.4.513.
BACKGROUND
Colorectal adenomatous and, probably, hyperplastic polyp development requires epithelial remodelling and stratification, with loss of E-cadherin expression implicated in adenoma formation. We have shown that P-cadherin, normally expressed in stratified epithelia and placenta, is aberrantly expressed in disturbed epithelial architecture associated with colitis.
AIMS
(i) To investigate the role of P-cadherin in colonic polyp formation. (ii) To ascertain whether expression of P-cadherin is independent of or correlated with expression of its associated proteins--E-cadherin, beta-catenin, and gamma-catenin. (iii) To determine if P-cadherin is functional regarding catenin binding in polyps.
METHODS
Expression and localisation of cadherins (E- and P-) and their associated catenins (beta- and gamma-) were determined in aberrant crypt foci (ACF), in polyps with hyperplastic morphology (hyperplastic polyps and serrated adenomas), and in adenomatous polyps by immunohistochemistry, western blotting, and mRNA in situ hybridisation. Assessment of cadherin-catenin binding was evaluated by co-immunoprecipitation. Adenomatous polyposis coli (APC) mutation was assessed in adenomatous polyps.
RESULTS
P-cadherin was expressed from ACF through to hyperplastic and adenomatous polyps. Alterations in E-cadherin and catenin expression occurred later, with variant patterns in (i) ACF, (ii) hyperplastic polyps and serrated adenomas, and (iii) adenomatous polyps. P-cadherin present in adenomas was functional with regard to catenin binding, and its expression was independent of APC mutational status.
CONCLUSIONS
P-cadherin is aberrantly expressed from the earliest morphologically identifiable stage of colonocyte transformation, prior to changes in E-cadherin, catenin, and APC expression/mutation. P-cadherin expression alone does not predict tissue morphology, and such expression is independent of that of associated cadherins and catenins.
背景
结直肠腺瘤性息肉以及可能的增生性息肉的发生需要上皮重塑和分层，E-钙黏蛋白表达缺失与腺瘤形成有关。我们已经表明，P-钙黏蛋白通常表达于复层上皮和胎盘中，在与结肠炎相关的紊乱上皮结构中异常表达。
目的
（i）研究P-钙黏蛋白在结肠息肉形成中的作用。（ii）确定P-钙黏蛋白的表达是否独立于或与其相关蛋白——E-钙黏蛋白、β-连环蛋白和γ-连环蛋白的表达相关。（iii）确定P-钙黏蛋白在息肉中与连环蛋白结合方面是否具有功能。
方法
通过免疫组织化学、蛋白质印迹法和mRNA原位杂交，在异常隐窝灶（ACF）、具有增生形态的息肉（增生性息肉和锯齿状腺瘤）以及腺瘤性息肉中，确定钙黏蛋白（E-和P-）及其相关连环蛋白（β-和γ-）的表达和定位。通过免疫共沉淀评估钙黏蛋白-连环蛋白结合情况。在腺瘤性息肉中评估腺瘤性息肉病（APC）突变情况。
结果
从ACF到增生性息肉和腺瘤性息肉均有P-钙黏蛋白表达。E-钙黏蛋白和连环蛋白表达的改变出现较晚，在（i）ACF、（ii）增生性息肉和锯齿状腺瘤以及（iii）腺瘤性息肉中有不同的模式。腺瘤中存在的P-钙黏蛋白在连环蛋白结合方面具有功能，其表达独立于APC突变状态。
结论
在E-钙黏蛋白、连环蛋白和APC表达/突变改变之前，P-钙黏蛋白在结肠细胞转化最早的形态学可识别阶段即异常表达。单独的P-钙黏蛋白表达不能预测组织形态，且这种表达独立于相关钙黏蛋白和连环蛋白的表达。
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