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信号转导与转录激活因子3（STAT3）介导CD44（+）CD24（- /低）乳腺癌干细胞在体外对他莫昔芬的耐药性。

STAT3 mediates resistance of CD44(+)CD24(-/low) breast cancer stem cells to tamoxifen in vitro.

作者信息

Wang Xiaoyan, Wang Guozhu, Zhao Yi, Liu Xiaoan, Ding Qiang, Shi Jingping, Ding Yin, Wang Shui

机构信息

Department of Breast Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China;

出版信息

J Biomed Res. 2012 Sep;26(5):325-35. doi: 10.7555/JBR.26.20110050. Epub 2012 Apr 18.

DOI:10.7555/JBR.26.20110050
PMID:23554768
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3597778/
Abstract

We sought to determine whether STAT3 mediated tamoxifen resistance of breast cancer stem cells in vitro. The capacities for mammosphere formation and STAT3 expression of CD44(+)CD24(-/low) MCF-7 and MCF-7 were observed. The CD44(+)CD24(-/low) subpopulation ratio and its sensitivity to adriamycin were analyzed in MCF-7 and TAM resistant (TAM-R) cells. Cell cycle, apoptosis, STAT3 and phospho-STAT3 changes were observed after treatment with tamoxifen. Small interference RNA-mediated knockdown of STAT3 in TAM-R cells was also performed. CD44(+)CD24(-/low) MCF-7 showed higher capacities for mammosphere formation and STAT3 expression than total MCF-7. The CD44(+)CD24(-/low) subpopulation was also upregulated in TAM-R cells with less sensitivity to adriamycin than MCF-7. Cell cycle changes, anti-apoptotic effects and STAT3 changes were also found. Meanwhile, the knock-down of STAT3 in TAM-R resulted in an increase in sensitivity to tamoxifen. It is concluded that STAT3 plays an essential role in breast cancer stem cells, which correlated with tamoxifen resistance.

摘要

我们试图在体外确定信号转导和转录激活因子3（STAT3）是否介导乳腺癌干细胞对他莫昔芬的耐药性。观察了CD44(+)CD24(-/低)MCF-7和MCF-7形成乳腺球的能力以及STAT3的表达。分析了MCF-7和他莫昔芬耐药（TAM-R）细胞中CD44(+)CD24(-/低)亚群比例及其对阿霉素的敏感性。用他莫昔芬处理后，观察细胞周期、凋亡、STAT3和磷酸化STAT3的变化。还在TAM-R细胞中进行了小干扰RNA介导的STAT3敲低。CD44(+)CD24(-/低)MCF-7形成乳腺球的能力和STAT3表达高于总的MCF-7。在TAM-R细胞中，CD44(+)CD24(-/低)亚群也上调，其对阿霉素的敏感性低于MCF-7。还发现了细胞周期变化、抗凋亡作用和STAT3变化。同时，TAM-R细胞中STAT3的敲低导致对他莫昔芬的敏感性增加。结论是，STAT3在乳腺癌干细胞中起重要作用，这与他莫昔芬耐药相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35fc/3597778/9c3f804f91e6/jbr-26-05-325-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35fc/3597778/8b4bff93d4fa/jbr-26-05-325-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35fc/3597778/a682da81bffe/jbr-26-05-325-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35fc/3597778/d887e79817ea/jbr-26-05-325-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35fc/3597778/ea352b5a24a6/jbr-26-05-325-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35fc/3597778/d95840d5c2be/jbr-26-05-325-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35fc/3597778/9c3f804f91e6/jbr-26-05-325-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35fc/3597778/8b4bff93d4fa/jbr-26-05-325-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35fc/3597778/a682da81bffe/jbr-26-05-325-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35fc/3597778/d887e79817ea/jbr-26-05-325-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35fc/3597778/ea352b5a24a6/jbr-26-05-325-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35fc/3597778/d95840d5c2be/jbr-26-05-325-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35fc/3597778/9c3f804f91e6/jbr-26-05-325-g006.jpg

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