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Xiaoyan Wang,Guozhu Wang,Yi Zhao,Xiaoan Liu,Qiang Ding,Jingping Shi,Yin Ding,Shui Wang.Journal of Biomedical Research,2012,26(5):/span>
STAT3 mediates resistance of CD44+CD24-/low breast cancer stem cells to tamoxifen in vitro
Received:May 10, 2011
DOI:10.7555/JBR.26.20110050
KeywordsSTAT3, breast cancer, cancer stem cells, tamoxifen drug resistance
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Xiaoyan Wang Department of Breast Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu , China
Guozhu Wang Department of Breast Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu , China
Yi Zhao Department of Breast Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu , China
Xiaoan Liu Department of Breast Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu , China
Qiang Ding Department of Breast Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu , China
Jingping Shi Department of Breast Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu , China
Yin Ding Laboratory of Mesoscopic Chemistry and Department of Polymer Science and Engineering, College of Chemistry and Chemical Engineering, Nanjing University, Nanjing, Jiangsu , China.
Shui Wang Department of Breast Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu , China
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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 rsistant (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.
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