c-Src介导的ERα与EGFR互作关系在乳腺癌三苯氧胺耐药中的作用  

Role of c-Src mediated interactional relationship between ERα and EGFR in tamoxifen resistance of breast cancer

作　　者：胡浩[1] 顾元龙[1] 钱毅[1] 朱从元[1] 李建平[1] 

机构地区：[1]江苏省无锡市第三人民医院普通外科,江苏无锡214041

出　　处：《中国普通外科杂志》2014年第5期618-623,共6页China Journal of General Surgery

基　　金：江苏省无锡市卫生局科研资助项目(XM1010)

摘　　要：目的:探讨雌激素受体(ER)与表皮生长因子受体(EGFR)的关系及其在乳腺癌三苯氧胺(TAM)治疗耐药中的作用与机制。方法:选用TAM治疗敏感(TAM-S)与耐药(TAM-R)的两种人乳腺癌MCF-7细胞,用免疫沉淀(IP)法检测ERα和EGFR在两种细胞中的结合情况,以及c-Src与前两者的结合情况,并用Western blot法检测两种细胞中c-Src的磷酸化水平;c-Src阻滞剂PP2处理两种细胞后,IP法再次检测ERα和EGFR结合情况。结果:ERα和EGFR在两种细胞中均以复合物的形式结合,但在TAM-R细胞中的结合量明显高于TAM-S细胞(P<0.05);c-Src与ERα、EGFR在两种细胞中均以复合物的形式结合,其磷酸化水平在TAM-R细胞中明显高于TAM-S细胞(P<0.05);PP2阻断c-Src的活性后,两种细胞中ERα和EGFR结合量均降低,且在TAM-R细胞中的降低程度明显大于TAM-S细胞(P<0.05)。结论:ERα和EGFR之间存在结合的现象,且两者的互作关系可能在乳腺癌TAM治疗耐药中起了重要作用,而c-Src的活化(磷酸化)是可能是介导了两者结合的关键机制。Objective： To investigate the relationship between estrogen receptor （ER） and epidermal growth factor receptor （EGFR）, and its role and mechanism in tamoxifen （TAM） therapy resistance of breast cancer.Methods： Two types of cells namely the TAM therapy-sensitive （TAM-S） and -resistant （TAM-R） human breast cancer MCF-7 cells were used. In these two types of cells, immunoprecipitation （IP） was performed to detect the connection between ERα and EGFR, and the connection of c-Src to the two former receptors, and the phosphorylation level of c-Src was also determined by Western blot analysis. After treatment with c-Src inhibitor PP2, the connection between ERα and EGFR was examined again by IP method. Results： ERα and EGFR linked in a complex form in both types of cells, but the linkage level in TAM-R cells was significantly higher than that in TAM-S cells （P〈0.05）. c-Src linked in a complex form to either ERα or EGFR in both types of cells, and the phosphorylation level of c-Src in TAM-R cells was significantly higher than that in TAM-S cells （P〈0.05）. After the c-Src activity was inhibited by PP2, linkage level between ERα or EGFR was decreased in both types of cells, while the decreasing degree in TAM-R cells was significantly greater than that in TAM-S cells （P〈0.05）.Conclusion： There is a connection between ERα and EGFR, which may play an important role in TAM therapy resistance of breast cancer, and c-Src activation （phosphorylation） may be the crucial mechanism for their linkage.

关 键 词：乳腺肿瘤 雌激素受体Α 受体 表皮生长因子 原癌基因蛋白质pp60(c-Src) 他莫昔芬 抗药性 肿瘤 

分 类 号：R737.9[医药卫生—肿瘤]