Survivin transcription is associated with P-glycoprotein/MDR1 overexpression in the multidrug resistance of MCF-7 breast cancer cells
Survivin transcription is associated with P-glycoprotein/MDR1 overexpression in the multidrug resistance of MCF-7 breast cancer cells
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Survivin转录与MCF-7乳腺癌细胞多药耐药性中P-糖蛋白/MDR1过表达相关
DOI：
10.3892/or_00000786
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发表时间：
2010-05-01
期刊：
影响因子：
4.2
通讯作者：
Jiang, Yuyang
中科院分区：
文献类型：
--
作者：
Liu, Feng;Liu, Shiying;Jiang, Yuyang
乳腺癌是女性最常见的恶性肿瘤。肿瘤的进展与凋亡抑制蛋白（inhibitors of apoptosis proteins，IAP）如生存素（survivin）和多药耐药P-糖蛋白（multidrug resistant P-glycoprotein，P-gp）的过度表达有关。PI 3 K/Akt信号通路参与细胞周期进程、凋亡和肿瘤转化。PI 3 K/Akt已被证明在乳腺癌中调节生存素。本研究旨在探讨Survivin和P-gp在MCF-7乳腺癌细胞和耐阿霉素（ADR）的MCF-7/ADR细胞中的表达及P-gp对Survivin在PI 3 K/Akt中表达的调节作用。经RT-PCR和Western blot检测，MCF-7/ADR细胞中survivin和P-gp的表达均高于MCF-7细胞。启动子活性分析显示Survivin转录与P-糖蛋白/MDR 1过表达相关。PI 3 K特异性抑制剂LY 294002可抑制survivin和P-gp的表达，降低survivin启动子活性，增强细胞对药物的敏感性。本研究表明，MCF-7乳腺癌多药耐药细胞中survivin的转录与P-gp/MDR 1的过度表达有关，PI 3 k/Akt通路参与了P-gp/MDR 1相关的survivin转录活性。
Breast carcinoma is the most common malignancy in women. The progression of tumor is associated with overexpression of inhibitors of apoptosis proteins (IAPs) such as survivin and multidrug resistant P-glycoprotein (P-gp). PI3K/Akt pathway is involved in cell cycle progression, apoptosis and neoplastic transformation. PI3K/Akt has been shown to regulate survivin in breast cancer. The aim of this study was to investigate the expression of survivin and P-gp, the modulation of survivin by P-gp in PI3K/Akt during the progression of drug resistance (MDR) in MCF-7 breast cancer cells and adriamycin (ADR)-resistant MCF-7/ADR cells. The expression of survivin and P-gp in MCF-7/ADR cells were higher than that of the MCF-7 cells using RT-PCR and Western blot analysis. Survivin transcription was associated with P-glycoprotein/MDR1 overexpression using promoter activity analysis. LY294002, specific inhibitor of PI3K could suppress survivin and P-gp expression, decreased survivin promoter activity and enhanced cell sensitivity to drugs. This study shows survivin transcription was associated with P-glycoprotein/MDR1 overexpression, PI3k/Akt pathway was involved in P-glycoprotein/MDR1 associated survivin transcription activity in the multidrug resistant MCF-7 breast cancer cells.