Slug and Pcad protein levels were strongly correlated along this timeline ( R =0.69, P <0.05). Western blot analysis showed a transient and significant decrease in Slug but also in Pcad protein levels (Figures 1c and d), culminating around 48 h. Slug repression resulted in a significant decrease of Pcad expression detected by rtPCR analysis (Figure 1b). We transfected mammary epithelial CommaD cells with SiRNAs targeting Slug. This was confirmed by rtPCR from Slug-KO mammary glands (Figure 1b) showing a striking Pcad downregulation. Myoepithelial cells appeared normal, based on smooth muscle actin and cytokeratin 5 (CK5) expression. Immunostaining showed a marked downregulation of Pcad in the basal layer of Slug-KO mammary tubules (Figure 1a). We looked at Pcad expression pattern in Slug-KO mammary gland. Slug controls Pcad gene expression in mouse mammary gland Here, we scrutinized possible links between Slug and Pcad in mammary gland and breast cancer. Pcad promotes collective cell migration and is correlated with poor prognosis in breast cancer. These cadherins can partially compensate each other in mediating cell-cell adhesion. Correct expression pattern is required for tubulogenesis. In mammary gland, Ecad is mostly expressed by luminal epithelial cells, whereas P-cadherin (Pcad) is exclusively expressed by basal/myoepithelial cells, similarly to Slug. The best defined target, E-cadherin (Ecad), is downregulated in Slug-overexpressing transformed cell lines. However, few direct transcriptional targets have been well characterized. Slug is also linked to invasiveness and to basal cell phenotype in human breast carcinoma. As an EMT transcription factor (EMT-TF) gene, Slug is known to induce cell-cell dissociation, motility and morphogenesis in distinct cell types. In brief, Slug appeared to control stem/progenitor cell dynamics. We defined distinct functions for Slug in cell proliferation, differentiation and survival. Recently, we and others described how Slug/Snail2, a member of the snail family of epithelial-mesenchymal transition (EMT) genes, was required for proper mammary tubulogenesis. Author(s): Y Idoux-Gillet M Nassour E Lakis F Bonini C Theillet S Du Manoir P Savagner Ĭomplex signaling pathways orchestrate breast morphogenesis.
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