ArticleBreast cancer research : BCR2013
Parity induces differentiation and reduces Wnt/Notch signaling ratio and proliferation potential of basal stem/progenitor cells isolated from mouse mammary epithelium.
Article in Breast cancer research : BCR, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.
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Who cites it
65 citing papers in PubMed, 1 synthesis or guideline pooled it, 96 citations in OpenAlex.
- Opioid use and the risk of cancer incidence and mortality: a systematic review.Cancer metastasis reviews · 2025Pooled it
- Effects of exposure to ethinyl estradiol during pregnancy and lactation on the postinvolution mammary gland.Journal of the Endocrine Society · 2026Article
- Pleiotrophin in Mammary Gland Development and Breast Cancer: A Comprehensive Review of the Evidence.Cells · 2026Review
- Divergent aging of nulliparous and parous mammary glands reveals IL33+ hybrid epithelial cells.Nature communications · 2026Article
- Parity modifies the effect of genetic variants associated with gestational duration and birth weight.medRxiv : the preprint server for health sciences · 2025Article
- Understanding Susceptibility to Breast Cancer: From Risk Factors to Prevention Strategies.International journal of molecular sciences · 2025Review
- Microfibril-associated protein 2 interacts with LEF1/TCF7 and immune infiltration in uterine corpus endometrial carcinoma.Central-European journal of immunology · 2025Article
- Epigenetic and Immune Mechanisms Linking Breastfeeding to Lower Breast Cancer Rates.Medical science monitor : international medical journal of experimental and clinical research · 2024Review
- Luminal Rank loss decreases cell fitness leading to basal cell bipotency in parous mammary glands.Nature communications · 2023Article
- Oncobiology and treatment of breast cancer in young women.Cancer metastasis reviews · 2022Review
- Examining the etiology of early-onset breast cancer in the Canadian Partnership for Tomorrow's Health (CanPath).Cancer causes & control : CCC · 2021Article
- Mammary Development and Breast Cancer: a Notch Perspective.Journal of mammary gland biology and neoplasia · 2021Review
- WNT4 Balances Development vs Disease in Gynecologic Tissues and Women's Health.Endocrinology · 2021Review
- Exposure to Propylparaben During Pregnancy and Lactation Induces Long-Term Alterations to the Mammary Gland in Mice.Endocrinology · 2021Article
- Prolactin synergizes with canonical Wnt signals to drive development of ER+ mammary tumors via activation of the Notch pathway.Cancer letters · 2021Article
- Estrogen Regulation of mTOR Signaling and Mitochondrial Function in Invasive Lobular Carcinoma Cell Lines Requires WNT4.Cancers · 2020Article
- Key steps for effective breast cancer prevention.Nature reviews. Cancer · 2020Review
- Wnt family member 4 (WNT4) and WNT3A activate cell-autonomous Wnt signaling independent of porcupineThe Journal of biological chemistry · 2019Article
- β-hCG-induced mutant BRCA1 ignites drug resistance in susceptible breast tissue.Carcinogenesis · 2019Article
- Environmental exposures during windows of susceptibility for breast cancer: a framework for prevention research.Breast cancer research : BCR · 2019Review
5 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
introductionEarly 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.
methodsMammary 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.
resultsTranscriptome 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.
conclusionsBy 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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