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. 2014 Oct 28;9(10):e111442. doi: 10.1371/journal.pone.0111442

Figure 4. Breast progenitor activity is expanded through non-hormonal and hormonal mechanisms.

Figure 4

(A) 17β-estradiol (E2) increased the expression of WNT3A, WNT4, and WNT8A in mammospheres compared to those treated with vehicle (n = 6 patient samples, mean±s.d.). Differences were detected by qPCR. (B) Progesterone (P4) increased the expression of WNT4 and WNT11 in mammospheres compared to those treated with vehicle (n = 6 patient samples, mean±s.d.). Differences were detected by qPCR. (C, D) shLRP6 mammary epithelial cells (MECs) demonstrated reduced acinar colony formation compared to shscram MECs when grown as single cells (C), or in suspension prior to plating on collagen (D), and E2 did not augment progenitor activity. E2 significantly increased acinar colony formation in shscram MECs compared to vehicle (n = 6 patient samples; mean±s.e.m.). (E) P4 increased ductal colony formation in shTBX3 MECs when grown as single cells or as mammospheres prior to plating on collagen (n = 6 patient samples; mean±s.e.m.). (F) shLRP6 MECs demonstrated decreased ductal colonies compared to shscram MECs on collagen. P4 did not enhance ductal colonies in shLRP6 MECs compared with vehicle (n = 6 patient samples; mean±s.e.m.). Reduction of LRP6 expression resulted in single cells with stellate projections instead of the growth of ductal colonies. (G) P4 treatment increased ductal colonies in WNT1 MECs compared with vehicle-treated cells (n = 6 patient samples; mean±s.e.m.). (H) TBX3 mediates non-hormonal growth through the secretion of WNT ligands. These ligands bind to LRP6 receptors on ductal progenitor cells as well as LRP6 receptors on acinar progenitor cells to coordinate the expansion of the two lineages for ductal/lobule formation. In response to hormones, cells expressing ERα and PR in luminal cells or PR in basal cells secrete WNT ligands to link the expansion of the two progenitor lineages for ductal/lobule formation in response to the cyclic changes of hormones during the menstrual cycle or pregnancy. Scale bar = 100 µm.