Overexpression and involvement of special AT-rich sequence binding protein 1 in multidrug resistance in human breast carcinoma cells
Overexpression and involvement of special AT-rich sequence binding protein 1 in multidrug resistance in human breast carcinoma cells
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DOI：
10.1111/j.1349-7006.2009.01372.x
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发表时间：
2010-01-01
期刊：
影响因子：
5.7
通讯作者：
Xu, Zu-De
中科院分区：
文献类型：
--
作者：
Li, Qing-Quan;Chen, Zhong-Qing;Xu, Zu-De
特殊的富含AT的序列结合蛋白（SATB）1已被提出作为一个决定因素，通过控制一组特定的基因，促进转移活性的表达，转移活性的收购。在这里，我们发现SATB 1表达在多药耐药乳腺癌细胞中上调，这些细胞表现出比亲本细胞更高的侵袭潜力。除了加速转移和诱导上皮-间质转化外，SATB 1被证明对MCF 7细胞的P-糖蛋白相关和P-糖蛋白非相关药物具有抗性，这伴随着SATB 1过表达转染子中阿霉素的积累减少。SATB 1缺失可部分逆转MCF 7/ADR的多药耐药表型。SATB 1诱导的P-糖蛋白介导的MDR可被抗P-糖蛋白mAb逆转。此外，SATB 1在MCF 7/ADR细胞中对阿霉素处理的抗凋亡活性中起重要作用，这提示了促成SATB 1相关的乳腺癌MDR的另一机制。这些数据为乳腺肿瘤获得MDR表型的模式提供了新的见解，也暗示了SATB 1在这一过程中的作用。（Cancer Sci 2009）。
Special AT-rich sequence binding protein (SATB) 1 has been proposed to act as a determinant for the acquisition of metastatic activity by controlling expression of a specific set of genes that promote metastatic activity. Here we found that SATB1 expression is upregulated in multidrug-resistant breast cancer cells that exhibit higher invasive potential than the parental cells. Apart from accelerating metastasis and inducing epithelial-mesenchymal transition, SATB1 was demonstrated to confer resistance to both P-glycoprotein-related and P-glycoprotein-non-related drugs on MCF7 cells, which was accompanied by decreasing accumulation of adriamycin in SATB1-overexpressing transfectants. SATB1 depletion could partially reverse the multidrug resistance (MDR) phenotype of MCF7/ADR in vitro and in vivo. The SATB1-induced P-glycoprotein-mediated MDR could be reversed by treatment with anti-P-glycoprotein mAb. Moreover, SATB1 plays an important role in anti-apoptotic activity in MCF7/ADR cells in response to adriamycin treatment, which suggests another mechanism contributing to SATB1-related MDR of breast cancers. These data provide new insights into the mode by which breast tumors acquire the MDR phenotype and also imply a role for SATB1 in this process. (Cancer Sci 2009).