摘要
目的:观察他莫昔芬耐药乳腺癌细胞BCAR3的表达与上皮间质转化(EMT)现象和乳腺癌的迁移侵袭的关系。探讨他莫昔芬耐药和乳腺癌细胞EMT现象的相关性。方法:以实时定量PCR和Western blot检测乳腺癌上皮样和间质样细胞系中BCAR3的表达;Western blot检测乳腺癌MCF-7、MCF-BCAR3和BT-549中介导EMT发生的转录因子Twist、上皮性标记基因E-钙黏素(E-cadherin)和间质性标记基因N-钙黏素(N-cadherin)表达的改变情况。Transwell侵袭实验检测乳腺癌MCF-7、MCF-BCAR3和BT-549侵袭转移能力。结果:BCAR3在乳腺癌上皮样细胞系中的表达明显低于间质样细胞系;E-cadherin蛋白在MCF-7细胞中的表达为阳性,Twist和N-cadherin表达为阴性;他莫昔芬耐药的细胞MCF-BCAR3 E-cadherin蛋白表达缺失,而Twist和N-cadherin表达阳性。BCAR3过度表达导致乳腺癌细胞MCF-7迁移和侵袭能力增强。结论:过度表达BCAR3增强乳腺癌细胞迁移和侵袭能力,并对他莫昔芬治疗产生耐药,可能与BCAR3诱导乳腺癌上皮间质转化有关。
Objective： To investigate the role of breast cancer anti-estrogen resistance-3（BCAR3） in epithelial-mesenchymal transition（EMT） induction of tamoxifen resistant of breast cancer cells,and to determine the relationship between BCAR3 induced tamoxifen resistance and invasiven metastatic behaviors.Methods： Real time PCR and Western blot were used to detect BCAR3 expression levels in epithelium and mesenchymal like breast cancer cell lines.The expression levels of E-cadherin,N-cadherin,and Twist were assessed by Western blot in MCF-7,MCF-BCAR3,and BT-549 cancer cells.Transwell migratory and invasive assays were employed to detect BCAR3 overexpression induced cell migration and invasion.Results： BCAR3 was expressed at higher levels in mesenchymal like-than in epithelial like-breast cancer cell lines.Stable over-expression of BCAR3 in MCF-7 cells leads to downregulation of E-cadherin expression and upregulation of Twist and N-cadherin expression.Coincidently in cells with relatively low migratory potential,BCAR3 overexpression resulted in enhanced migration and invasion.Conclusion： During the development of tamoxifen resistance,BCAR3 may regulate breast cell migration by promotion of EMT,thereby coordinates multiple signaling pathways.
出处
《武汉大学学报（医学版）》
CAS
北大核心
2010年第4期471-475,共5页
Medical Journal of Wuhan University
关键词
乳腺癌
他莫昔芬耐药
BCAR3
上皮间质转化
侵袭
Breast Cancer
Tamoxifen Resistance
BCAR3
Epithelial-Mesenchymal Transition
Invasion
