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Keywords {🔍}

cells, mammary, cell, basal, mice, stemprogenitor, wnt, epithelial, parous, pubmed, signaling, luminal, article, google, scholar, subpopulations, virgin, figure, expression, gene, breast, sca, decrease, stem, cancer, cas, switzerland, krt, analysis, pregnancy, genes, data, control, parity, agematched, file, early, parityinduced, additional, proliferation, total, central, isolated, gland, mmm, differentiation, wntnotch, subpopulation, effect, myoepithelial,

Topics {✒️}

wnt/beta-catenin-responsive stem cells anti-guinea pig ig-alexa488 balwierz & erik van nimwegen poly-l-lysine-coated slides basal stem/progenitor-cell subpopulation mohamed bentires-alj lef1/tcf7 transcription factor fewest parity-induced gene-expression estrogen/progesterone receptor-positive cells facs-sorted mammary stromal anti-rabbit ig-alexa546 estrogen/progesterone-sensitive luminal cells mammary stem/progenitor cells krt18/krt14 double-positivity decreased biotinylated anti-rabbit igg basal stem/progenitor cells family-wise error rate early parity-induced gene-expression age-matched virgin control article download pdf full-term pregnancy induces wnt/notch signaling ratio transcription-factor binding sites transcription-factor binding motif genome-wide expression profiles fluorescence-activated cell sorting cell subtype-specific fashion freshly sorted cells wnt transcription-factor activities bentires-alj lab age-matched virgin controls primary anti-mouse antibodies luminal cell-fate commitment progesterone receptor-positive cells article meier-abt taqman probe-based system specific cell-surface markers balb/c-trp53+/- mice polystyrene cell-culture flasks higher-order cell clumps age-matched virgin mice hormone receptor-positive cells p21-positive epithelial cells wnt/notch signaling pathways entire breasts/mammary glands d'cruz cm decreased wnt/notch signaling highest colony-formation capacity gene-expression profiling data wnt4-secreting luminal cells

Questions {❓}

• Thordarson G, Jin E, Guzman RC, Swanson SM, Nandi S, Talamantes F: Refractoriness to mammary tumorigenesis in parous rats: is it caused by persistent changes in the hormonal environment or permanent biochemical alterations in the mammary epithelia?

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         headline:Parity induces differentiation and reduces Wnt/Notch signaling ratio and proliferation potential of basal stem/progenitor cells isolated from mouse mammary epithelium
         description:Early pregnancy has a strong protective effect against breast cancer in humans and rodents, but the underlying mechanism is unknown. Because breast cancers are thought to arise from specific cell subpopulations of mammary epithelia, we studied the effect of parity on the transcriptome and the differentiation/proliferation potential of specific luminal and basal mammary cells in mice. Mammary epithelial cell subpopulations (luminal Sca1-, luminal Sca1+, basal stem/progenitor, and basal myoepithelial cells) were isolated by flow cytometry from parous and age-matched virgin mice and examined by using a combination of unbiased genomics, bioinformatics, in vitro colony formation, and in vivo limiting dilution transplantation assays. Specific findings were further investigated with immunohistochemistry in entire glands of parous and age-matched virgin mice. Transcriptome analysis revealed an upregulation of differentiation genes and a marked decrease in the Wnt/Notch signaling ratio in basal stem/progenitor cells of parous mice. Separate bioinformatics analyses showed reduced activity for the canonical Wnt transcription factor LEF1/TCF7 and increased activity for the Wnt repressor TCF3. This finding was specific for basal stem/progenitor cells and was associated with downregulation of potentially carcinogenic pathways and a reduction in the proliferation potential of this cell subpopulation in vitro and in vivo. As a possible mechanism for decreased Wnt signaling in basal stem/progenitor cells, we found a more than threefold reduction in the expression of the secreted Wnt ligand Wnt4 in total mammary cells from parous mice, which corresponded to a similar decrease in the proportion of Wnt4-secreting and estrogen/progesterone receptor-positive cells. Because recombinant Wnt4 rescued the proliferation defect of basal stem/progenitor cells in vitro, reduced Wnt4 secretion appears to be causally related to parity-induced alterations of basal stem/progenitor cell properties in mice. By revealing that parity induces differentiation and downregulates the Wnt/Notch signaling ratio and the in vitro and in vivo proliferation potential of basal stem/progenitor cells in mice, our study sheds light on the long-term consequences of an early pregnancy. Furthermore, it opens the door to future studies assessing whether inhibitors of the Wnt pathway may be used to mimic the parity-induced protective effect against breast cancer.
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      headline:Parity induces differentiation and reduces Wnt/Notch signaling ratio and proliferation potential of basal stem/progenitor cells isolated from mouse mammary epithelium
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         Mammary Epithelial Cell
         Cell Subpopulation
         Signaling Ratio
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         Cancer Research
         Oncology
         Surgical Oncology
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      name:Mechanisms of Cancer, Friedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland
      name:Mechanisms of Cancer, Friedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland
      name:Mechanisms of Cancer, Friedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland
      name:Philosophical Natural Sciences, University of Basel, Basel, Switzerland
      name:Mechanisms of Cancer, Friedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland
      name:Biozentrum, University of Basel, Basel, Switzerland
      name:Biozentrum, University of Basel, Basel, Switzerland
      name:Mechanisms of Cancer, Friedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland

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