一个新的促进人胰腺癌细胞上皮-间充质转化因子:ATF-2

ATF2,a novel factor promoting epithelial-mesenchymal transition in human pancreatic cancer cells

目的:研究活化转录因子2(activating transcription factor-2,ATF2)在人胰腺癌细胞系Capan2 中高表达能否促使转化生长因子β1(transforming growth factor-β1,TGF-β1)诱导Capan2细胞上皮-间充质转化(epithelial-mesenchymal transition,EMT).方法:应用PGEX-ATF2质粒瞬时转染Capan2 细胞系,并继续用TGF-β1诱导,以仅加DMSO 组为空白对照组,倒置显微镜观察细胞形态学变化,Western blot检测E-cadherin、vimentin、ATF2的表达. Transwell小室侵袭实验验证侵袭能力的变化.结果:与空白对照组细胞相比,转染ATF2并用 TGF-β1诱导的Capan2细胞系能够明显改变细胞形态,并且使得E-cadherin的蛋白水平表达明显下调,vimentin、ATF2的蛋白水平表达则显著上调,细胞侵袭能力也显著增加(P=0.008).结论:ATF2能够与TGF-β1联合共同诱导 Capan2细胞系产生EMT,从而对胰腺癌的分子靶向治疗找到新的方向.

AIM： To investigate whether ATF2 together with TGF-β1 can induce epithelial-mesenchymal tran- sition （EMT） in human pancreatic cancer cell line Capan2. METHODS： Capan2 cells were induced with TGF-β1 after transfection with PGEX-ATF2, and the negative control group was treated with DMSO. Cell morphological alternations were examined by phase contrast microscopy. The ex- pression of mesenchymal marker vimentin andepithelial markers E-cadherin and ATF2 were detected by Western blot. Cell migration was determined by Transwell motility assay. RESULTS： Compare to the negative control group, cells transfected with ATF2 and treated with TGF-β1 showed loss of cell-cell contacts, fi- broblastic morphology, decreased expression of E-cadherin, up-regulated expression of vimentin and ATF2, and increased migration ability （P = 0.008）. CONCLUSION： ATF2 together with TGF-β1 can induce EMT in human pancreatic cancer cell line Capan2. ATF2 may be a new molecular target for therapy of pancreatic cancer.