STAT3 mediates resistance of CD44+CD24−/low breast cancer stem cells to tamoxifen in vitro

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.

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