Human scribble accumulates in colorectal neoplasia in association with an altered distribution of β-catenin
Human scribble accumulates in colorectal neoplasia in association with an altered distribution of β-catenin
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DOI：
10.1016/j.humpath.2007.01.026
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发表时间：
2007-08-01
期刊：
影响因子：
3.3
通讯作者：
Abe, Yasuhito
中科院分区：
文献类型：
--
作者：
Kamei, Yoshiaki;Kito, Katsumi;Abe, Yasuhito
上皮极性和组织结构的丧失是恶性肿瘤的诊断特征。在果蝇中，遗传学研究确定了3个肿瘤抑制基因（nTSGs）， nTSGs的缺失已被证明会导致上皮细胞顶基极性的破坏和肿瘤生长。Scribble是果蝇nTSGs的一种，它编码一种含有多pdz结构域的膜相关细胞质蛋白。与果蝇相比，其哺乳动物同源物的致癌作用尚未确定。本文采用亲和纯化抗体，免疫组织化学方法检测hScrib蛋白在人结直肠肿瘤组织中的分布。在50例结直肠腺瘤和腺癌中，与邻近正常上皮相比，常见hScrib蛋白的积累。此外，hScrib的过表达和分布与ss-catenin的细胞质积累广泛重叠。与ss-catenin一样，hScrib在小腺瘤中也常表现出强烈的免疫反应性，提示hScrib可能参与结肠癌发生的早期阶段。5个相应的肝转移灶与其原发部位相比显示出相当的抗hscrib免疫反应性。在培养细胞系的免疫荧光分析中，根据ss-catenin的细胞质易位，观察到hScrib的膜性染色丢失。我们在此证明，hScrib蛋白的积累可能参与结肠癌的发生，同时也提供了hScrib和ss-catenin之间的可能联系。(c) 2007爱思唯尔公司版权所有。
The loss of epithelial polarity and tissue architecture is a diagnostic feature of malignant tumors. In Drosophila, genetic studies identified 3 neoplastic tumor suppressor genes (nTSGs), and a loss of nTSGs has been shown to result in a disruption of apical-basal polarity and neoplastic growth in epithelial cells. Scribble is one type of the Drosophila nTSGs, which encodes a membrane-associated cytoplasmic protein containing the multi-PDZ domain. In contrast to Drosophila scribble, the oncogenic roles of its mammalian homologues have not yet been established. We herein immunohistochemically examined the distributions of hScrib protein in human colorectal neoplasia using affinity-purified antibody. In 50 cases of colorectal adenomas and adenocarcinomas, the accumulation of hScrib protein was commonly observed in comparison with the adjacent normal epithelia. Furthermore, the overexpression and distribution of hScrib was observed to extensively overlap with the cytoplasmic accumulation of ss-catenin. Like ss-catenin, the intense immunoreactivity of hScrib was often observed in small adenomas, thus, suggesting that hScrib could be involved in an early step of colon carcinogenesis. Five corresponding liver metastases showed a comparable immunoreactivity for anti-hScrib in comparison with their primary sites. In an immunofluorescence analysis on cultured cell lines, the loss of membranous staining of hScrib was observed according to the cytoplasmic translocation of ss-catenin. We herein demonstrate that the accumulation of hScrib protein might therefore be involved in colon carcinogenesis while also providing a possible link between hScrib and ss-catenin. (c) 2007 Elsevier Inc. All rights reserved.