Cytoplasmic expression of epithelial cell transforming sequence 2 in lung adenocarcinoma and its implications for malignant progression
Cytoplasmic expression of epithelial cell transforming sequence 2 in lung adenocarcinoma and its implications for malignant progression
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DOI：
10.1038/s41374-018-0142-4
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发表时间：
2019-04-01
影响因子：
5
通讯作者：
Noguchi, Masayuki
中科院分区：
文献类型：
--
作者：
Kosibaty, Zeinab;Murata, Yoshihiko;Noguchi, Masayuki
上皮细胞转化序列2（ECT2）是一种鸟嘌呤核苷酸交换因子，主要定位于非转化细胞的细胞核中，其功能是调节胞质分裂。ECT2也定位于癌细胞的细胞质中。ECT2的异常细胞质表达被认为驱动肿瘤生长和侵袭。在这项研究中，我们研究了ECT2在肺腺癌细胞质中的表达及其预后和生物学意义。对细胞核和细胞质的细胞组分进行Western印迹，以确定ECT2在肺腺癌细胞系中的亚细胞定位。应用免疫组化方法检测167例肺腺癌组织中ECT2的表达，并应用Kaplan-Meier曲线和考克斯回归分析其临床意义。对13例新鲜肺腺癌刮片细胞学标本进行ECT2亚细胞定位及其Thr790磷酸化（P-ECT2（T790））检测。我们发现，ECT2定位于细胞核和细胞质的肺腺癌细胞株和肿瘤组织。免疫组化法检测83例（50%）肺腺癌细胞胞浆中ECT2表达，发现在癌症进展过程中ECT2表达增加。30例（29%）小腺癌（
Epithelial cell transforming sequence 2 (ECT2), a guanine nucleotide exchange factor, is predominantly localized in the nucleus of non-transformed cells and functions to regulate cytokinesis. ECT2 is also localized in the cytoplasm of cancer cells. Aberrant cytoplasmic expression of ECT2 is thought to drive tumor growth and invasion. In this study, we investigated the cytoplasmic expression of ECT2 and its prognostic and biological significance in lung adenocarcinoma. Western blotting of cellular fractions from the nucleus and cytoplasm was performed to determine the subcellular localization of ECT2 in lung adenocarcinoma cell lines. The cytoplasmic expression of ECT2 in 167 lung adenocarcinomas was evaluated by immunohistochemistry and its clinical significance was examined using Kaplan-Meier curves and Cox regression analysis. Scraping cytology specimens of 13 fresh lung adenocarcinomas were used to assess the subcellular localization of ECT2 and its phosphorylation at Thr790 (P-ECT2(T790)). We found that ECT2 was localized in both the nucleus and cytoplasm of lung adenocarcinoma cell lines and tumor tissues. Cytoplasmic expression of ECT2 was detected by immunohistochemistry in 83 (50%) of the lung adenocarcinomas, and was found to increase during cancer progression. It was expressed in 30 (29%) small adenocarcinomas (