Erschienen in:
01.09.2014 | Brief Report
Exosomal miR-221/222 enhances tamoxifen resistance in recipient ER-positive breast cancer cells
verfasst von:
Yifang Wei, Xiaofeng Lai, Shentong Yu, Suning Chen, Yongzheng Ma, Yuan Zhang, Huichen Li, Xingmei Zhu, Libo Yao, Jian Zhang
Erschienen in:
Breast Cancer Research and Treatment
|
Ausgabe 2/2014
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Abstract
Recent studies have demonstrated that specific miRNAs, such as miR-221/222, may be responsible for tamoxifen resistance in breast cancer. Secreted miRNAs enclosed in exosomes can act as intercellular bio-messengers. Our objective is to investigate the role of secreted miR-221/222 in tamoxifen resistance of ER-positive breast cancer cells. Transmission electron microscopy analysis and nanoparticle tracking analysis were performed to determine the exosomes difference between MCF-7TamR (tamoxifen resistant) and MCF-7wt (tamoxifen sensitive) cells. PKH67 fluorescent labeling assay was used to detect exosomes derived from MCF-7TamR cells entering into MCF-7wt cells. The potential function of exosomes on tamoxifen resistance transmission was analyzed with cell viability, apoptosis ,and colony formation. MiRNA microarrays and qPCR were used to detect and compare the miRNAs expression levels in the two cells and exosomes. As the targets of miR-221/222, p27 and ERα were analyzed with western blot and qPCR. Compared with the MCF-7wt exosomes, there were significant differences in the concentration and size distribution of MCF-7TamR exosomes. MCF-7wt cells had an increased amount of exosomal RNA and proteins compared with MCF-7TamR cells. MCF-7TamR exosomes could enter into MCF-7wt cells, and then released miR-221/222. And the elevated miR-221/222 effectively reduced the target genes expression of P27 and ERα, which enhanced tamoxifen resistance in recipient cells. Our results are the first to show that secreted miR-221/222 serves as signaling molecules to mediate communication of tamoxifen resistance.