转化生长因子-β_1协同转录因子Snail促进乳腺癌转移  

Transforming growth factors-β_1 cooperating with transcriptional factor Snail promotes breast tumor metastasis

作　　者：张阿丽[1] 王全胜[2] 钟亚华[1] 陈刚[3] 奚玲[3] 谢丛华[1] 周云峰[1] 马丁[3] 

机构地区：[1]武汉大学中南医院放化疗科,湖北武汉430071 [2]华中科技大学同济医学院附属协和医院中医科,湖北武汉430022 [3]华中科技大学同济医学院附属同济医院妇产科,湖北武汉430030

出　　处：《中国药理学通报》2007年第10期1317-1321,共5页Chinese Pharmacological Bulletin

基　　金：国家重点基础研究发展计划(973计划)资助项目(No2002CB513100)

摘　　要：目的研究表明转录因子Snail是肿瘤转移重要的调节因子,但关于影响Snail调节作用的因素及相应的信号转导通路研究较少。该研究探讨转化生长因子-β1(transforming growth factor-β1,TGF-β1)与转录因子Snail调节乳腺癌细胞转移潜能及可能机制。方法选用乳腺上皮性癌细胞株MCF-7为研究对象,构建正义与反义Snail的腺病毒载体,应用相差显微镜观察细胞形态的变化;应用Boyden小室体外侵袭实验检测癌细胞体外转移潜能;应用Western蛋白印迹检测细胞免疫表型的改变及TGF-β1调节转录因子Snail表达过程中对MAPK、PI3K信号通路的影响。结果TGF-β1、Snail均能使MCF-7细胞伪足增多、增长,细胞体外侵袭力增强,且两者有协同作用;TGF-β1可以刺激Snail及间质标记基因FN、MMP-2、RhoA蛋白表达,同时活化ERK、Akt且其活化有一定的时间依赖性;反义Snail能抑制TGF-β1对ERK、Akt信号通路的活化。结论TGF-β1通过增加Snail、FN、MMP-2、RhoA蛋白的表达和活化ERK、Akt信号通路而促进乳腺癌细胞转移潜能的增强;并且TGF-β1的这种作用能被反义Snail所拮抗。Aim It was reported that transcriptional factor Snail is the important gene modulating tumor metastasis, but there was few reports about the relationship between Snail and the cellular factors. This study was designed to observe the role of Snail and transforming growth factor-β1（ TGF-β1） in breast tumor metastasis. Methods After transfected with Snail cDNA or treated with TGF-β1, the morphology of breast tumor cell MCF-7 was observed under microscope;the capacity of metastasis in vitro was examined by Boyden chamber assay; the activation of mesenchymal genes such as FN, MMP-2, RhoA as well as signal pathways MAPK and PI3K was analyzed by Western blot. Results The cell invasion ability was induced by TGF-β1 or Snail cDNA, accompanied with the more and longer cellular pseudopod （ compared with the control, P 〈 0.05 ） ; the Snail, FN, MMP-2 and RhoA proteins expression and the activity of ERK and Akt increased in the TGF-β1 groups time-dependently; after transfected with antisense Snail, the added TGF-β1 failed to increase the above proteins expression as well as the activities of ERK and Akt. Conclusions TGF-β1 can increase the breast tumor metastasis through stimulating the expression of Snail, FN, MMP-2, RhoA and activating the ERK and Akt pathways, while the effect of TGF-β1 can be prevented by antisense Snail.

关 键 词：肿瘤转移 TGF—β1 SNAIL 

分 类 号：R329.25[医药卫生—人体解剖和组织胚胎学] R341.31[医药卫生—基础医学]