HER3影响辐照诱导的Luminal A型乳腺癌细胞的迁移和侵袭

HER3 affects irradiation-induced migration and invasion in Luminal A breast cancer cells

目的:探讨敲低人表皮生长因子受体-3(human epidermal growth factor receptor-3,HER3)表达及联合辐照对Luminal A型乳腺癌细胞迁移和侵袭能力的影响及分子机制。方法:利用短发夹RNA(sh RNA)稳定转染乳腺癌细胞MCF-7和ZR75-1,敲低HER3表达。蛋白免疫印迹实验(Western blot)检测细胞转染效率。将转染空病毒的对照组(sh RNA-Control)与HER3敲低组(sh RNA-HER3)细胞进行6-Gy X线辐照,细胞划痕实验及侵袭实验(Transwell assay)分析各组乳腺癌细胞迁移和侵袭能力。Western blot检测紧密连接蛋白Claudin-1的表达变化。结果:敲低HER3后,乳腺癌细胞MCF-7和ZR75-1内HER3蛋白表达水平明显降低。单纯辐照的乳腺癌细胞,迁移和侵袭能力增强,Claudin-1蛋白表达增加;而敲低HER3及联合辐照后,乳腺癌细胞迁移和侵袭能力降低,Claudin-1蛋白表达明显降低。结论:敲低HER3表达可以降低辐照诱导的luminal A型乳腺癌细胞的迁移和侵袭能力,其机制可能通过下调紧密连接蛋白Claudin-1的表达而实现。

Objective：To investigate the effect of knockdown of human epidermal growth factor receptor-3（HER3）expression on migration and invasion with irradiation（IR）in breast cancer cells and its molecular mechanism. Methods：Stable transfected breast cancer cells MCF-7 and ZR75-1 were established by short hairpin RNA（sh RNA）to knockdown the expression of HER3 gene. The transfection efficiency was detected by Western blot. The control group transfected with empty virus and HER3 knockdown group were irradiated by 6-Gy X-ray. Cell healing assay and Transwell assay were used to analyze the migration and invasion ability of breast cancer cells. Western blot was used to detect the expression of Claudin-1. Results：After knockdown of HER3,HER3 protein expression in MCF-7 and ZR75-1 cells was significantly decreased. After IR,the migration and invasion increased,and the expression of Claudin-1 protein increased. However,knockdown of HER3 and combined IR reduced the migration and invasion of breast cancer cells,and decreased the expression of Claudin-1. Conclusion：Knockdown of HER3 reduces the migration and invasion of Luminal A breast cancer cells after IR. Its mechanism may be through the down-regulation of Claudin-1 expression.