PLK1调控Pin1促进乳腺癌对他莫昔芬耐药的机制  

PLK1 regulates Pin1 to promote tamoxifen resistance in breast cancer

作　　者：陈阳[1] 姚燕丹[2] 罗曼莉[3] 黄松音[1] CHEN Yang1, YAO Yan-dan2, LUO Man-li3, HUANG Song-yin1(1.Department of Laboratory, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120; 2.Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120; 3. Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, Chin)

机构地区：[1]中山大学孙逸仙纪念医院检验科,广东广州510120 [2]中山大学孙逸仙纪念医院乳腺肿瘤医学部,广东广州510120 [3]中山大学孙逸仙纪念医院医学研究中心,广东广州510120

出　　处：《热带医学杂志》2018年第3期294-297,共4页Journal of Tropical Medicine

基　　金：国家自然科学基金(81572890;81772837);广东省科技社会发展项目(2014A050503029);逸仙科研启航项目(YXQH201701)

摘　　要：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 Pinl 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. Pin 1 mRNA level was detected by quantitative PCR. PLK1, phospho-PLK1 and Pinl protein level were detected by western blot. Co-immunoprecipitation assay was used to detect the interaction relationship between Pinl and PLK1 in vitro, siPLK1 and PLK1 inhibitor BI2536/BI6727 was used to degrade PLK1 or inhibit its function. Results Pinl, PLK1 and phospho-PLK1 protein was overexpressed in MCF-TR eel1, for 3.1, 1.3 and 2.4 folds, respectively. The co-immunoprecipitation assay result indicated that PLK1 was interacted with Pinl in vitro, and knockdown PLK1 by siRNA or block its function by BI2536/BI6727 could both lead to the decrease in Pinl protein level. Conclusion PLK1 interacted with Pinl and regulated its protein level in TAM-R breast cancer cells.

关 键 词：PLK1 PIN1 乳腺癌 他莫昔芬耐药 

分 类 号：R737.9[医药卫生—肿瘤]