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-东南大学学报医学版

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

单位：贵州医科大学附属肿瘤医院乳腺外科, 贵州贵阳 550003

分类号：R737.9

出版年·卷·期（页码）：2022·41·第四期（498-504）

摘要：

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.

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