Fig. 2

Progesterone receptor mediated induction of the WNT/RANKL-driven mitotic signal in mammary epithelial cells. a Heat map showing differentially expressed genes (adjusted p value < 0.05) between Sham and EP and EP vs EP + PR inhibitor in MaSC, LP, and LM cells. b In RNA-seq data, LP cells show highest induction of Wnt4/Rankl-driven signal in EP-treated group. c, d qRTPCR was performed to confirm the downstream signaling of Wnt4/Rankl across all cell lineages. Livak’s fold change was calculated relative to MaSC (Sham). c A significant induction of Wnt4 expression was observed in LP and LM cells upon EP exposure relative to Sham (p < 0.0001); this effect was not observed in mice treated with EP + PR inhibitors, LP (p < 0.0001), LM EP + TPA (p < 0.01), and LM EP + MFP (p < 0.001). d LP cells in EP-treated mice show a strong induction of Rankl/Tnfsf11 (p < 0.0001). This induction was not observed in mice group treated with EP + PR inhibitors (p < 0.0001). LM cells in EP-treated mice also show significant albeit lesser induction of Rankl/Tnfsf11 (p < 0.05) and was reversed in EP + PR inhibitor-treated mice (p < 0.05). The MaSC compartment showed a non-significant induction of Rankl/Tnfsf11 signaling (p > 0.05). e Lrp5 expression was significantly induced in all three lineages after treatment with EP relative to sham (p < 0.0001) and suppressed in EP + PR inhibitor-treated mice (p < 0.0001). f Axin2 mRNA expression is significantly induced (p < 0.001) in EP-treated group in MSC and LP cells relative to sham, which is abrogated in mice treated with EP + PR inhibitors (p < 0.0001). g Mmp7 mRNA expression was induced both LP and LM cells in EP-treated mice compared to sham group (p < 0.0001), and this effect was reversed in EP + PR inhibitor-treated mice (p < 0.0001). MaSc cells show a significant induction of Mmp7 expression (p < 0.05) in EP group relative to sham group and this effect is reversed in mice treated with EP + PR inhibitors (p < 0.05)