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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> |
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STAT3 mediates resistance of CD44+CD24-/low breast cancer stem cells to tamoxifen in vitro |
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Received:May 10, 2011
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DOI:10.7555/JBR.26.20110050
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Keywords:STAT3, breast cancer, cancer stem cells, tamoxifen drug resistance
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Grant Program:
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Author |
Institution |
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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