驱动蛋白家族成员15在非特殊型浸润性乳腺癌中的表达及意义

Expression and significance of KIF15 in non-special invasive breast cancer

目的:探讨驱动蛋白家族成员15(KIF15)在非特殊型浸润性乳腺癌(IC-NST)中的表达及意义。方法:免疫组织化学法检测126例IC-NST癌组织及配对癌旁组织、80例导管内癌组织中KIF15的表达。蛋白质印迹法检测正常乳腺细胞(MCF-10A)和乳腺癌细胞(MDA-MB-231和MCF-7)中KIF15蛋白的表达。分析KIF15与临床预后的关系。采用RNA干扰技术沉默MDA-MB-231和MCF-7细胞中KIF15的表达,观察细胞增殖、侵袭、凋亡及Notch1信号通路相关蛋白(hes1、hes5、NICD)的变化。CCK-8法检测细胞增殖活力,Transwell实验检测细胞侵袭能力,Annexin-V-FITC/PI流式细胞术检测细胞凋亡。结果:IC-NST癌组织中KIF15阳性表达率为70.63%(89/126),高于导管内癌组织[38.75%(31/80),P<0.05]和癌旁组织[23.01%(29/126),P<0.05]。乳腺癌MDA-MB-231和MCF-7细胞的KIF15蛋白表达水平分别为1.89±0.34、1.33±0.21,均高于正常乳腺细胞MCF-10A(0.29±0.10,P<0.05)。KIF15表达是IC-NST患者无进展生存时间的影响因素(HR=1.562,95%CI 1.200~7.298,P<0.05)。沉默KIF15基因后MDA-MB-231、MCF-7细胞的增殖和侵袭力均受到抑制,而凋亡水平升高(P<0.05)。沉默KIF15基因后MDA-MB-231、MCF-7细胞的hes1、hes5、NICD蛋白表达水平均下降(P<0.05)。结论:KIF15在IC-NST中高表达,与患者不良生存预后有关。沉默KIF15基因后乳腺癌细胞的增殖、侵袭均受到抑制,凋亡水平升高。

Objective:To explore the expression and significance of kinesin superfamily 15(KIF15)in non-specific invasive breast cancer(IC-NST).Methods:Immunohistochemistry was used to detect the expression of KIF15 in 126 IC-NST cancer tissues and paired adjacent tissues,and 80 intraductal cancer tissues.The protein expression of KIF15 in normal breast cells(MCF-10A)and breast cancer cells(MDA-MB-231 and MCF-7)were detected by Western-blot.The relationship between KIF15 and clinical prognosis was analyzed.RNA interference technology was used to silence the expression of KIF15 in MDA-MB-231 and MCF-7 cells,and the changes of cell proliferation,invasion,apoptosis and Notch1 signaling pathway related proteins(hes1,hes5,NICD)were observed.Cell proliferation activity were detected by CCK-8 method;cell invasion ability were detected by Transwell experiment;cell apoptosis were detected by Annexin-V-FITC/PI flow cytometry.Results:The positive expression rate of KIF15 in IC-NST cancer tissue was 70.63%(89/126),which was higher than that in ductal cancer tissue[38.75%(31/80),P<0.05]and adjacent tissues[23.01%(29/126),P<0.05].The expression levels of KIF15 protein in breast cancer MDA-MB-231 and MCF-7 cells were 1.89±0.34 and 1.33±0.21,respectively,which were higher than that of normal breast cells MCF-10A(0.29±0.10,P<0.05).The expression of KIF15 was an influencing factor for the progression-free survival time of IC-NST patients(HR=1.562,95%CI 1.200-7.298,P<0.05).After silencing the KIF15 gene,the proliferation and invasiveness of MDA-MB-231 and MCF-7 cells were inhibited,while the level of apoptosis increased(P<0.05).After silencing the KIF15 gene,the protein expression levels of hes1,hes5 and NICD in MDA-MB-231 and MCF-7 cells decreased(P<0.05).Conclusion:KIF15 is highly expressed in IC-NST,which is related to the poor survival prognosis of patients.After silencing the KIF15 gene,the proliferation and invasion of breast cancer cells are inhibited,and the level of apoptosis increases.