Estradiol, TGF-1 and hypoxia promote breast cancer stemness and EMT-mediated breast cancer migration

Breast cancer is one of the most common cancer types among women, acting as a distinct cause of mortality, and has a high incidence of recurrence. External stimuli, including 17-estradiol (E2), transforming growth factor (TGF)-1 and hypoxia, may be important in breast cancer growth and metastasis. However, the effects of these stimuli on breast cancer stem cell (CSC) regulation have not been fully investigated. In the present study, the proportion of cluster of differentiation (CD)44(+)/CD24(-/low) cells increased following treatment with E2, TGF-1 and hypoxia in MCF-7 cells. The expression of CSC markers, including SOX2, KLF4 and ABCG2, was upregulated continually by E2, TGF-1 and hypoxia. In addition, the expression levels of epithelial-mesenchymal transition-associated factors increased following treatment with E2, TGF-1 and hypoxia. Therefore, the migration ability of E2-, TGF-1- and hypoxia-treated MCF-7 cells was enhanced compared with control cells. In addition, the enhancement of apoptosis by 5-flurouracil or radiation was abolished following treatment with E2, TGF-1 and hypoxia. These results indicate that E2, TGF-1 and hypoxia are important for regulating breast CSCs, and that the modulation of the microenvironment in tumors may improve the efficiency of breast cancer therapy.