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Egr-1 通过增加胃癌中的β-catenin 表达促进细胞增殖和侵袭。

Egr-1 promotes cell proliferation and invasion by increasing β-catenin expression in gastric cancer.

机构信息

Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, China.

出版信息

Dig Dis Sci. 2013 Feb;58(2):423-30. doi: 10.1007/s10620-012-2356-4. Epub 2012 Aug 24.

DOI:10.1007/s10620-012-2356-4
PMID:22918686
Abstract

BACKGROUND

Abnormal expression of early growth response gene 1 (Egr-1) and β-catenin may play a crucial role in the development and progression of human cancer. However, little is known about the expression and underlying molecular mechanisms in which Egr-1 and β-catenin are involved in the development and progression of gastric cancer.

AIMS

The purpose of this study was to elucidate the potential relationship between Egr-1 and β-catenin expression in gastric cancer, which contributes to finding new molecular carcinogenesis as a potential therapeutic target for gastric cancer.

METHODS

In a sample of 102 cases of human gastric cancer, the expression of Egr-1 and β-catenin was detected using immunohistochemistry. Egr-1 gene was transfected into gastric cancer SGC7901 cells and its role in proliferation and cell invasion was detected by MTT assay, flow cytometry, wound-healing and transwell invasion assay. Western blot analysis was used to study the expression of β-catenin and cyclin D1 proteins.

RESULTS

Upregulated Egr-1 and β-catenin protein expression were strongly correlated with cancer progression and depth of invasion in gastric cancer. β-catenin, present mainly in cytoplasmic and nucleus of gastric cancer cells, was also positively correlated with Egr-1 expression in gastric cancer. Furthermore, the overexpression of Egr-1 upregulated β-catenin expression level, promoted cell proliferation, increased cell population in S-phase and enhanced gastric cancer cell migration and invasion in vitro.

CONCLUSIONS

Egr-1 might contribute to gastric cancer proliferation and invasion through activation of the β-catenin signaling pathway.

摘要

背景

早期生长反应基因 1(Egr-1)和β-连环蛋白的异常表达可能在人类癌症的发生和发展中起关键作用。然而,Egr-1 和β-连环蛋白在胃癌的发生和发展中表达及其潜在的分子机制知之甚少。

目的

本研究旨在阐明胃癌中 Egr-1 和β-连环蛋白表达之间的潜在关系,以期发现新的分子致癌机制,为胃癌的潜在治疗靶点提供依据。

方法

采用免疫组织化学法检测 102 例人胃癌组织中 Egr-1 和β-连环蛋白的表达。用 Egr-1 基因转染胃癌 SGC7901 细胞,MTT 法、流式细胞术、划痕愈合实验和 Transwell 侵袭实验检测 Egr-1 对细胞增殖和侵袭的影响,Western blot 分析检测β-连环蛋白和细胞周期蛋白 D1 蛋白的表达。

结果

Egr-1 和β-连环蛋白蛋白表达上调与胃癌的进展和浸润深度密切相关。β-连环蛋白主要存在于胃癌细胞的细胞质和细胞核中,在胃癌中与 Egr-1 的表达呈正相关。此外,Egr-1 的过表达上调了β-连环蛋白的表达水平,促进了细胞增殖,增加了 S 期细胞群,并增强了胃癌细胞的体外迁移和侵袭能力。

结论

Egr-1 可能通过激活β-连环蛋白信号通路促进胃癌的增殖和侵袭。

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