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环化酶相关蛋白 1(CAP1)表达下调可降低食管鳞癌细胞的迁移能力。

Downregulated expression of the cyclase-associated protein 1 (CAP1) reduces migration in esophageal squamous cell carcinoma.

机构信息

Department of Pathology, Affiliated Hospital of Nantong University, Jiangsu 226001, PR China.

出版信息

Jpn J Clin Oncol. 2013 Sep;43(9):856-64. doi: 10.1093/jjco/hyt093. Epub 2013 Jul 30.

DOI:10.1093/jjco/hyt093
PMID:23904342
Abstract

OBJECTIVE

Overexpression of cyclase-associated proteins has been associated with poor prognosis in several human cancers. Cyclase-associated protein 1 is a member of the cyclase-associated proteins which contributes to tumor progression. The aim of the present study was to examine the expression of cyclase-associated protein 1 and to elucidate its clinicopathologic significance in a larger series of esophageal squamous cell carcinoma.

METHODS

Immunohistochemical and western blot analyses were performed in esophageal squamous cell carcinoma tissues. Survival analyses were performed by using the Kaplan-Meier method. The role of cyclase-associated protein 1 in migration was studied in esophageal squamous cell carcinoma cell lines of TE1 through knocking down cyclase-associated protein 1 with siRNA and overexpression of cyclase-associated protein 1. The regulation of cyclase-associated protein 1 on migration was determined by transwell and wound-healing assays.

RESULTS

Immunohistochemical analysis showed that cyclase-associated protein 1 expression was negatively associated with E-cadherin and significantly associated with lymph node metastases. Survival analysis revealed that cyclase-associated protein 1 overexpression was significantly associated with overall survival (P = 0.011). Knock down of cyclase-associated protein 1 in TE1 cells resulted in decreased vimentin and F-actin levels and the capability for migration. In addition, overexpression of cyclase-associated protein 1 promoted the migration of TE1 cells.

CONCLUSIONS

These findings suggest that cyclase-associated protein 1 is involved in the metastasis of esophageal squamous cell carcinoma, and that elevated levels of cyclase-associated protein 1 expression may indicate a poor prognosis for patients with esophageal squamous cell carcinoma.

摘要

目的

环化酶相关蛋白的过表达与几种人类癌症的不良预后相关。环化酶相关蛋白 1 是环化酶相关蛋白家族的成员之一,有助于肿瘤的进展。本研究旨在检测环化酶相关蛋白 1 在更大系列食管鳞癌中的表达,并阐明其临床病理意义。

方法

采用免疫组织化学和 Western blot 分析检测食管鳞癌组织中 cyclase-associated protein 1 的表达。采用 Kaplan-Meier 法进行生存分析。通过 siRNA 敲低 cyclase-associated protein 1 和过表达 cyclase-associated protein 1 研究 cyclase-associated protein 1 在食管鳞癌细胞系 TE1 中的迁移作用。通过 Transwell 和划痕愈合实验确定 cyclase-associated protein 1 对迁移的调节作用。

结果

免疫组织化学分析表明,cyclase-associated protein 1 的表达与 E-钙黏蛋白呈负相关,与淋巴结转移显著相关。生存分析显示,cyclase-associated protein 1 的过表达与总生存期显著相关(P=0.011)。在 TE1 细胞中敲低 cyclase-associated protein 1 导致波形蛋白和 F-肌动蛋白水平降低和迁移能力下降。此外,过表达 cyclase-associated protein 1 促进了 TE1 细胞的迁移。

结论

这些发现表明 cyclase-associated protein 1 参与了食管鳞癌的转移,cyclase-associated protein 1 表达水平升高可能预示着食管鳞癌患者预后不良。

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