Anxa2 Plays a Critical Role in Enhanced Invasiveness of the Multidrug Resistant Human Breast Cancer Cells
Anxa2 Plays a Critical Role in Enhanced Invasiveness of the Multidrug Resistant Human Breast Cancer Cells
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Anxa2 在增强多药耐药人类乳腺癌细胞的侵袭性方面发挥关键作用
DOI：
10.1021/pr900461c
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发表时间：
2009-11-01
影响因子：
4.4
通讯作者：
Niu, Ruifang
中科院分区：
文献类型：
--
作者：
Zhang, Fei;Zhang, Lin;Niu, Ruifang
多药耐药（Multidrug resistance，MDR）是肿瘤化疗失败的主要原因。最近的报道甚至认为MDR与肿瘤细胞的侵袭和转移有关。本研究采用蛋白质组学方法对多药耐药诱导的细胞迁移过程中起重要作用的基因进行了研究。采用2D-PAGE和MALDI-TOF/MS蛋白质组学方法对MCF-7和MCF-7/ADR（一种P-糖蛋白过表达的阿霉素耐药乳腺癌细胞系）之间差异表达的蛋白质进行了分离和鉴定。Annexin a2（Anxa 2）在MCF-7/ADR细胞中高表达，而在MCF-7细胞中不表达。小干扰RNA介导的基因抑制表明Anxa 2是MCF-7/ADR细胞增殖和侵袭所必需的。单独下调Anxa 2不足以逆转细胞对阿霉素的敏感性，表明Anxa 2不是MDR表型所必需的。总之，我们的结果表明，当癌细胞MCF-7获得耐药性时，Anxa 2的表达增强，并且它在MDR诱导的肿瘤侵袭中起重要作用。
Multidrug resistance (MDR) is the major cause of failure in cancer chemotherapy. Recent reports even suggest that MDR is associated with elevated invasion and metastasis of tumor cells. In the current study, we used a proteomic approach to identify genes that play an important role in MDR induced cell migration 2D-PAGE and MALDI-TOF/MS-based proteomics approach were used to separate and identify differentially expressed proteins between MCF-7 and MCF-7/ADR, a p-glycoprotein-overexpressing adnamycin-resistance breast cancer cell line. Annexin a2 (Anxa2) was identified as highly expressed in MCF-7/ADR cells, but not in MCF-7 cells Small interference RNA-mediated gene suppression demonstrated that Anxa2 was required for enhanced cell proliferation and invasion of the MCF-7/ADR cells. Down-regulation of Anxa2 alone was not sufficient to revert the cell sensitivity to adnamycin, suggesting that Anxa2 was not required for MDR phenotype Taken together, our results showed that expression of Anxa2 is enhanced when cancer cells, MCF-7, acquired drug resistance and it plays an essential role in MDR-induced tumor invasion