Analysis of Snail-1, E-cadherin and claudin-1 expression in colorectal adenomas and carcinomas.

Analysis of Snail-1, E-cadherin and claudin-1 expression in colorectal adenomas and carcinomas.
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DOI:
10.3390/ijms13021632
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发表时间:
2012
影响因子:
5.6
通讯作者:
Belej K
Belej K
中科院分区:
生物学2区
文献类型:
--
作者:
Bezdekova M;Brychtova S;Sedlakova E;Langova K;Brychta T;Belej K

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我们报告的表达Snail-1,E-cadherin和claudin-1的间接免疫组织化学在结肠肿瘤。Snail-1是一种锌指转录因子,在已经经历了几乎完全的上皮-间质转化(EMT)并且已经从肿瘤中逃逸的细胞中表达。Snail诱导EMT的主要机制是下调E-cadherin,其表达在许多不同类型的肿瘤中频繁下调,其中它伴随恶性细胞的侵袭和转移行为。此外,Snail-1可能下调claudin-1的表达,claudin-1是一种细胞-细胞粘附蛋白,在肿瘤发生期间的进展和传播中起着可能的作用。Snail-1在癌细胞和腺瘤细胞中表达,在邻近肿瘤的粘膜中具有组织学正常上皮,没有显著差异,并且主要是强染色强度。在亚细胞水平上,正常和肿瘤上皮之间显示出统计学显著性差异(p = 0.003),其中观察到蛋白质向细胞质的转移以及细胞质/细胞核或纯细胞质的组合表达。E-钙粘蛋白的表达存在于100%的腺癌和腺瘤的情况下,与占主导地位的强膜免疫反应性和肿瘤和正常粘膜的蛋白表达之间没有差异。在腺癌和腺瘤的肿瘤细胞中检测到claudin-1的主要强阳性。在蛋白质定位方面观察到显著差异,其中膜染色,典型的非肿瘤上皮,在腺癌(p = 0.0001)和腺瘤(0.0002)中变为膜/细胞质表达,其中细胞质移位与更高程度的异型增生相关。此外,与腺瘤(51%)相比,癌组(87%)中膜/胞质定位更常见(p = 0.0001)。我们得出结论,Snail-1和claudin-1的异位亚细胞定位可能参与细胞形态和行为的变化,这可能与改变蛋白质的有效途径有关,从而在很大程度上有助于癌症的发展。
We report the expression of Snail-1, E-cadherin and claudin-1 by indirect immunohistochemistry in colonic neoplasia. Snail-1 is a zinc finger transcription factor expressed in cells that already have undergone almost complete epithelial-mesenchymal transition (EMT) and have already evaded from the tumor. The main mechanism by which Snail induces EMT is downregulation of E-cadherin, of which expression was shown to be frequently downregulated in many different types of tumors, where it accompanies the invasiveness and metastatic behavior of malignant cells. Moreover, Snail-1 may downregulate the expression of claudin-1, a cell-cell adhesion protein which plays a likely role in progression and dissemination during tumorigenesis. Snail-1 was expressed in both carcinoma and adenoma cells with histologically normal epithelium in the mucosa, adjacent to the tumors, without significant differences, and predominant strong intensity of staining. Statistically significant differences were revealed between normal and tumorous epithelium (p = 0.003) at the subcellular level, where the shift of the protein to the cytoplasm with combined cytoplasmic/nuclear or pure cytoplasmic expression was observed. E-cadherin expression was present in 100% of cases of both adenocarcinomas and adenomas, with prevailing strong membranous immunoreactivity and no differences between protein expression in tumors and normal mucosa. Predominating strong positivity of claudin-1 was detected in tumor cells of adenocarcinomas and adenomas. Marked differences were seen in protein localization, where membranous staining, typical for nontumorous epithelium, changed to combined membranous/cytoplasmic expression in adenocarcinomas (p = 0.0001) and adenomas (0.0002), in which cytoplasmic shift was associated with a higher degree of dysplasia. Furthermore, membranous/cytoplasmic localization was more frequent in the carcinoma group (87%) in comparison with adenomas (51%) (p = 0.0001). We conclude that dystopic subcellular localizations of Snail-1 and claudin-1 may participate in changes of cellular morphology and behavior which might be associated with altered effectory pathways of proteins and thus substantially contribute to the cancer development.
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