TY - JOUR AB - It is believed that breast cancer stem cells (BCSCs), like normal stem cell counterparts, have the capacity of self-renewal and differentiation. Simultaneously, estrogen receptor (ER)-negative (-) BCSCs are affected by surrounding differentiated ER-positive (+) tumor cells by virtue of paracrine signaling within the tumor micro­environment. Genistein (GEN), as a sort of phytoestrogen, can act on ER+ breast cancer cells but the role of GEN in the differentiation of neighboring ER- BCSCs has not been defined. Transwell co-culture system was utilized so as to elaborate the interaction between well-differentiated ER+ breast cancer cells (MCF-7) and ER- breast cancer stem/progenitor cells (mammospheres derived from MDA-MB-231 cells). GEN-induced differentiation of BCSCs was analyzed by mammospheres formation assay, flow cytometry and RT-PCR after a 3 day solo-culture or co-culture. We find that GEN sized 2 µM, and 40 nM, effectively promotes morphological alteration of mammospheres, reduces the ratio of subset of CD44+/CD24-/ESA+ cells and upregulates the expression of differentiated cell markers of mammospheres in co-culture system, but not in solo-culture condition. Besides, we demonstrate that the differentiation-inducing effect of GEN on mammospheres is associated with PI3K/Akt and MEK/ERK signaling pathways which are activated by amphiregulin released from ER+ cancer cells. These results indicate that GEN was able to induce the differentiation of breast cancer stem/progenitor cells through interaction with ER+ cancer cells by a paracrine mechanism. AD - The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, P.R. China The Fifth Hospital of Harbin City, Harbin, Heilongjiang, P.R. China The Third Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, P.R. China The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, P.R. China AU - Liu,Yanchen AU - Zou,Tianbiao AU - Wang,Shuhuai AU - Chen,Hong AU - Su,Dongju AU - Fu,Xiaona AU - Zhang,Qingyuan AU - Kang,Xinmei DA - 2016/03/01 DO - 10.3892/ijo.2016.3351 EP - 1072 IS - 3 JO - Int J Oncol KW - genistein differentiation stem cells paracrine PY - 2016 SN - 1019-6439 1791-2423 SP - 1063 ST - Genistein-induced differentiation of breast cancer stem/progenitor cells through a paracrine mechanism T2 - International Journal of Oncology TI - Genistein-induced differentiation of breast cancer stem/progenitor cells through a paracrine mechanism UR - https://doi.org/10.3892/ijo.2016.3351 VL - 48 ER -