ITGB1通过激活MAPK/ERK通路促进前列腺癌细胞侵袭

Promotion of prostate cancer cell migration and invasion via activating MAPK/ERK signaling pathway by ITGB1

目的 研究ITGB1基因在前列腺癌中的表达情况及对前列腺癌细胞侵袭行为的影响和可能作用机制.方法 实时荧光定量PCR检测ITGB1在前列腺癌标本和前列腺癌细胞株PC3和LNCaP中的表达水平.设计小干扰RNA干扰ITGB1的表达,观察干扰效率以及干扰后对前列腺癌PC3和LNCaP细胞的迁移和侵袭能力的影响.结果 ITGB1 mRNA在前列腺癌标本中表达水平上调（t =5.12,P＜0.05）,在前列腺癌细胞株LNCaP和PC3中表达水平也较正常前列腺上皮高（P＜0.01）.siRNA成功干扰ITGB1表达后,划痕实验显示,前列腺癌Lncap和PC3细胞迁移能力显著下降.Transwell侵袭实验显示干扰ITGB1后,前列腺癌细胞的侵袭能力较对照组也显著下降.GCBI基因网络分析显示,ITGB1与MAPK通路具有显著相关性.进一步行蛋白质免疫印迹杂交实验显示,干扰ITGB1后,MAPK通路中ERK蛋白和磷酸化的ERK的蛋白表达下降,并且下游MMP9蛋白水平也呈现下降.结论 ITGB1通过激活MAPK信号通路,促进前列腺癌细胞迁移和侵袭.

Objectives To explore the expression of ITGB1 in prostate cancer tissues and cells and its role in the progression of prostate cancer.Methods Quanitative real time PCR was used to detect the expression of ITGB1 in prostate cancer tissues and cells.Silence of ITGB1 was performed by using small interference RNA （siRNA）.Mter silencing of ITGB 1,cell migration and invasion were detected to verify the function of ITGB1 on prostate cancer cells.Western Blot was performed to determine the changes of key modulators of MAPK/ERK pathways.Results According to the qRT-PCR results,ITGB1 mRNA significantly overexpressed in prostate cancer tissues （t =5.12,P 〈 0.05） and cells（P 〈 0.01）.Small interference RNA successfully down-regulated the expression of ITGB1 mRNA and protein in LNCaP and PC3 cells.Silence of ITGB1 could suppress cell migration of prostate cancer cells.In addition,cell invasion also could be repressed by silencing of ITGB1.Furthermore,the changes of key modulators of MAPK/ERK pathways were detected.Both ERK and p-ERK were downregulated by silencing ITGB1 when compared with control group.Also,the decrease of MMP9 protein after silencing of ITGB1 was found.Conclusions ITGB1 promotes cell migration and invasion of prostate cancer cell via activating MAPK/ERK pathway.