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FOXA1的过表达抑制人胃癌AGS细胞的增殖和上皮-间质转化。

Overexpression of FOXA1 inhibits cell proliferation and EMT of human gastric cancer AGS cells.

作者信息

Lin Mengxin, Pan Jie, Chen Qiang, Xu Zongbin, Lin Xiaoyan, Shi Chunmei

机构信息

Department of Oncology, Fujian Medical University Union Hospital, Fuzhou, Fujian Province 350001, China.

Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province 350001, China.

出版信息

Gene. 2018 Feb 5;642:145-151. doi: 10.1016/j.gene.2017.11.023. Epub 2017 Nov 10.

Abstract

The lack of effective medical treatment for advanced stages of gastric cancer mainly contributes to the high mortality rate. The association of forkhead box protein A1 (FOXA1) with tumor progression has been reported in different human cancers. However, the function of FOXA1 in gastric cancer is largely unknown. In the present study, FOXA1 protein showed a significant reduction in gastric cancer samples comparing with matched control samples. In addition, the higher expression of FOXA1 in transcription level was observed in gastric cancer cell lines as compared with that in normal gastric cell line, while the contrary result was observed in protein level. Then we studied the effects of FOXA1 on gastric cancer cells in vitro and in vivo based on FOXA1-overexpression AGS cells. We found that up-regulation of FOXA1 was notably inhibited the cell proliferation and tumor formation, and induced cell apoptosis. Moreover, overexpression of FOXA1 was able to increase the E-cadherin protein level and decreased the Vimentin protein level, which implicates that FOXA1 probably plays as an inhibitor of epithelial mesenchymal transition. In conclusion, these data suggests that FOXA1 may function as a novel anti-oncogene in gastric cancer cells.

摘要

晚期胃癌缺乏有效的医学治疗方法,这是导致其高死亡率的主要原因。叉头框蛋白A1(FOXA1)与不同人类癌症中的肿瘤进展之间的关联已有报道。然而,FOXA1在胃癌中的功能在很大程度上尚不清楚。在本研究中,与配对的对照样本相比,FOXA1蛋白在胃癌样本中显著减少。此外,与正常胃细胞系相比,在转录水平上观察到FOXA1在胃癌细胞系中表达较高,而在蛋白水平上观察到相反的结果。然后,我们基于过表达FOXA1的AGS细胞在体外和体内研究了FOXA1对胃癌细胞的影响。我们发现FOXA1的上调显著抑制了细胞增殖和肿瘤形成,并诱导了细胞凋亡。此外,FOXA1的过表达能够增加E-钙黏蛋白的蛋白水平并降低波形蛋白的蛋白水平,这表明FOXA1可能作为上皮-间质转化的抑制剂发挥作用。总之,这些数据表明FOXA1可能在胃癌细胞中作为一种新的抑癌基因发挥作用。

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