title: Estradiol, TGF-β1 and hypoxia promote breast cancer stemness and EMT-mediated breast cancer migration.
abstract: 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 17β-estradiol (E2), transforming growth factor (TGF)-β1 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-/lowcells increased following treatment with E2, TGF-β1 and hypoxia in MCF-7 cells. The expression of CSC markers, including SOX2, KLF4 and ABCG2, was upregulated continually by E2, TGF-β1 and hypoxia. In addition, the expression levels of epithelial-mesenchymal transition-associated factors increased following treatment with E2, TGF-β1 and hypoxia. Therefore, the migration ability of E2-, TGF-β1- 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-β1 and hypoxia. These results indicate that E2, TGF-β1 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.
authors.affiliation: Research Center, Dongnam Institute of Radiological and Medical Sciences, Busan 46033, Republic of Korea; Department of Pharmacy, Pusan National University, Busan 46241, Republic of Korea.
authors.forename: Seong-Joon
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Research Center, Dongnam Institute of Radiological and Medical Sciences, Busan 46033, Republic of Korea.
authors.forename: Joong-Gook
authors.initials: JG
authors.lastname: Kim
authors.affiliation: Department of Pharmacy, Pusan National University, Busan 46241, Republic of Korea.
authors.forename: Nam Deuk
authors.initials: ND
authors.lastname: Kim
authors.affiliation: Research Center, Dongnam Institute of Radiological and Medical Sciences, Busan 46033, Republic of Korea; Department of Radiation Oncology, Dongnam Institute of Radiological & Medical Sciences, Busan 46033, Republic of Korea; Department of Radiation Oncology, Korea Institute of Radiological & Medical Sciences, Seoul 01812, Republic of Korea.
authors.forename: Kwangmo
authors.initials: K
authors.lastname: Yang
authors.affiliation: Research Center, Dongnam Institute of Radiological and Medical Sciences, Busan 46033, Republic of Korea.
authors.forename: Jae Woong
authors.initials: JW
authors.lastname: Shim
authors.affiliation: Research Center, Dongnam Institute of Radiological and Medical Sciences, Busan 46033, Republic of Korea.
authors.forename: Kyu
authors.initials: K
authors.lastname: Heo
keywords: breast cancer stem cell; estrogen; hypoxia; transforming growth factor-β1