标题:ER-alpha 36-Mediated Rapid Estrogen Signaling Positively Regulates ER-Positive Breast Cancer Stem/Progenitor Cells
作者:Deng, Hao; Zhang, Xin-Tian; Wang, Mo-Lin; Zheng, Hong-Yan; Liu, Li-Jiang; Wang, Zhao-Yi
作者机构:[Deng, Hao; Zhang, Xin-Tian; Wang, Mo-Lin; Wang, Zhao-Yi] Creighton Univ, Sch Med, Dept Med Microbiol, Omaha, NE 68178 USA.; [Deng, Hao; Zhang, Xin- 更多
通讯作者:Wang, ZY
通讯作者地址:[Wang, ZY]Creighton Univ, Sch Med, Dept Med Microbiol, Omaha, NE 68178 USA.
来源:PLOS ONE
出版年:2014
卷:9
期:2
DOI:10.1371/journal.pone.0088034
摘要:The breast cancer stem cells (BCSC) play important roles in breast cancer occurrence, recurrence and metastasis. However, the role of estrogen signaling, a signaling pathway important in development and progression of breast cancer, in regulation of BCSC has not been well established. Previously, we identified and cloned a variant of estrogen receptor alpha, ER-alpha 36, with a molecular weight of 36 kDa. ER-alpha 36 lacks both transactivation domains AF-1 and AF-2 of the 66 kDa full-length ER-alpha (ER-alpha 66) and mediates rapid estrogen signaling to promote proliferation of breast cancer cells. In this study, we aim to investigate the function and the underlying mechanism of ER-alpha 36-mediated rapid estrogen signaling in growth regulation of the ER-positive breast cancer stem/progenitor cells. ER-positive breast cancer cells MCF7 and T47D as well as the variants with different levels of ER-alpha 36 expression were used. The effects of estrogen on BCSC's abilities of growth, self-renewal, differentiation and tumor-seeding were examined using tumorsphere formation, flow cytometry, indirect immunofluorence staining and in vivo xenograft assays. The underlying mechanisms were also studied with Western-blot analysis. We found that 17-beta-estradiol (E2 beta) treatment increased the population of ER-positive breast cancer stem/progenitor cells while failed to do so in the cells with knocked-down levels of ER-alpha 36 expression. Cells with forced expression of recombinant ER-alpha 36, however, responded strongly to E2 beta treatment by increasing growth in vitro and tumor-seeding efficiency in vivo. The rapid estrogen signaling via the AKT/GSK3 beta pathway is involved in estrogen-stimulated growth of ER-positive breast cancer stem/progenitor cells. We concluded that ER-alpha 36-mediated rapid estrogen signaling plays an important role in regulation and maintenance of ER-positive breast cancer stem/progenitor cells.
收录类别:SCIE
WOS核心被引频次:26
资源类型:期刊论文
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