ArticleStem cells (Dayton, Ohio)2011
Repression of mammary stem/progenitor cells by p53 is mediated by Notch and separable from apoptotic activity.
Article in Stem cells (Dayton, Ohio), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 68 citations in OpenAlex.
- Rewiring Cellular Context as A Central Mechanism Governing Cancer Stem Cell Survival: Insights from ESC Comparisons.Stem cell reviews and reports · 2026Review
- Article
- An Isoxazoloquinone Derivative Inhibits Tumor Growth by Targeting STAT3 and Triggering Its Ubiquitin-Dependent Degradation.Cancers · 2023Article
- p53 Inhibits Bmi-1-driven Self-Renewal and Defines Salivary Gland Cancer Stemness.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Exposure to Propylparaben During Pregnancy and Lactation Induces Long-Term Alterations to the Mammary Gland in Mice.Endocrinology · 2021Article
- The Radiation-Induced Regenerative Response of Adult Tissue-Specific Stem Cells: Models and Signaling Pathways.Cancers · 2021Review
- Unlocking the Secrets of Cancer Stem Cells with γ-Secretase Inhibitors: A Novel Anticancer Strategy.Molecules (Basel, Switzerland) · 2021Review
- Depletion of Trp53 and Cdkn2a Does Not Promote Self-Renewal in the Mammary Gland but Amplifies Proliferation Induced by TNF-α.Stem cell reports · 2021Article
- Systemic therapies for salivary gland adenoid cystic carcinoma.American journal of cancer research · 2021Review
- The effect of radiation on the ability of rat mammary cells to form mammospheres.Radiation and environmental biophysics · 2020Article
- Adverse outcome pathways for ionizing radiation and breast cancer involve direct and indirect DNA damage, oxidative stress, inflammation, genomic instability, and interaction with hormonal regulation of the breast.Archives of toxicology · 2020Review
- Cancer Stemness: p53 at the Wheel.Frontiers in oncology · 2020Review
- A clonal stem cell line established from a mouse mammary placode with ability to generate functional mammary glands.In vitro cellular & developmental biology. Animal · 2019Article
- Notch and breast cancer metastasis: Current knowledge, new sights and targeted therapy.Oncology letters · 2019Review
- p53 balances between tissue hierarchy and anarchy.Journal of molecular cell biology · 2019Review
- Functional Diversity of p53 in Human and Wild Animals.Frontiers in endocrinology · 2019Review
- Deconstructing networks of p53-mediated tumor suppression in vivo.Cell death and differentiation · 2018Review
- p53 and Cell Fate: Sensitizing Head and Neck Cancer Stem Cells to Chemotherapy.Critical reviews in oncogenesis · 2018Review
- Somatic loss of estrogen receptor beta and p53 synergize to induce breast tumorigenesis.Breast cancer research : BCR · 2017Article
- p53 deficiency induces cancer stem cell pool expansion in a mouse model of triple-negative breast tumors.Oncogene · 2017Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Breast cancer is the most common tumor among women with inherited mutations in the p53 gene (Li-Fraumeni syndrome). The tumors represent the basal-like subtype, which has been suggested to originate from mammary stem/progenitor cells. In mouse mammary epithelium, mammosphere-forming potential was increased with decreased dosage of the gene encoding the p53 tumor suppressor protein (Trp53). Limiting dilution transplantation also showed a 3.3-fold increase in the frequency of long-term regenerative mammary stem cells in Trp53-/- mice. The repression of mammospheres by p53 was apparent despite the absence of apoptotic responses to radiation indicating a dissociation of these two activities of p53. The effects of p53 on progenitor cells were also observed in TM40A cells using both mammosphere-forming assays and the DsRed-let7c-sensor. The frequency of long-term label-retaining epithelial cells was decreased in Trp53-/- mammary glands indicating that asymmetric segregation of DNA is diminished and contributes to the expansion of the mammary stem cells. Treatment with an inhibitor of γ-secretase (N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester) reduced the number of Trp53-/- mammospheres to the level found in Trp53+/+ cells. These results demonstrate that basal levels of p53 restrict mammary stem/progenitor cells through Notch and that the Notch pathway is a therapeutic target to prevent expansion of this vulnerable pool of cells.
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