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目的 探究Polo样激酶1(PLK1)对他莫昔芬耐药(TAM-R)乳腺癌中脯氨酰异构酶Pin1的调控机制.方法 长期低浓度加药法诱导TAM-R乳腺癌细胞系MCF-7R,采用荧光定量PCR、Western blot检测PLK1、p-PLK1、Pin1表达水平,应用免疫共沉淀技术证明PLK1和Pin1在细胞内相互作用,通过siRNA和PLK1抑制剂确认PLK1对于Pin1的调控作用.结果 他莫昔芬耐药乳腺癌细胞MCF-7R中,Pin1、PLK1、p-PLK1蛋白水平分别是亲本细胞MCF-7的3.1、1.3和2.4倍,差异有统计学意义(P<0.05).通过免疫共沉淀实验证明,PLK1和Pin1可以在细胞内相互作用,并且PLK1抑制剂或者siRNA显著减少Pin1蛋白表达水平.结论 TAM-R乳腺癌中PLK1与Pin1相互作用并能调控Pin1的蛋白水平.“,”Objective To study the regulatory mechanism of Pin1 in tamoxifen resistance breast cancer. Methods Tamoxifen-resitance breast cancer cell line MCF-7(MCF-7R)was generated by culturing for long period at low-dose of tamoxifen. Pin1 mRNA level was detected by quantitative PCR. PLK1,phospho-PLK1 and Pin1 protein level were detected by western blot. Co-immunoprecipitation assay was used to detect the interaction relationship between Pin1 and PLK1 in vitro. siPLK1 and PLK1 inhibitor BI2536/BI6727 was used to degrade PLK1 or inhibit its function. Results Pin1,PLK1 and phospho-PLK1 protein was overexpressed in MCF-7R cell,for 3.1,1.3 and 2.4 folds,respectively. The co-immunoprecipitation assay result indicated that PLK1 was interacted with Pin1 in vitro,and knockdown PLK1 by siRNA or block its function by BI2536/BI6727 could both lead to the decrease in Pin1 protein level. Conclusion PLK1 interacted with Pin1 and regulated its protein level in TAM-R breast cancer cells.