ArticleNucleic acids research2013
BRCA1 is a key regulator of breast differentiation through activation of Notch signalling with implications for anti-endocrine treatment of breast cancers.
Article in Nucleic acids research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 53 citations in OpenAlex.
- Proteomic Analysis of Invasive Breast Cancer Cells Treated with CBD Reveals Proteins Associated with the Reversal of Their Epithelial-Mesenchymal Transition Induced by IL-1β.International journal of molecular sciences · 2025Article
- RFX5 promotes the progression of triple-negative breast cancer through transcriptional activation of JAG1.Human cell · 2025Article
- Subtype-specific role for Jagged1 in promoting or inhibiting breast tumor formation.Oncogenesis · 2025Article
- The molecular features of lung cancer stem cells in dedifferentiation process-driven epigenetic alterations.The Journal of biological chemistry · 2024Review
- BRCA1 the Versatile Defender: Molecular to Environmental Perspectives.International journal of molecular sciences · 2023Review
- BRCA1 and NORE1A Form a Her2/Ras Regulated Tumor Suppressor Complex Modulating Senescence.Cancers · 2023Article
- R-Loops and R-Loop-Binding Proteins in Cancer Progression and Drug Resistance.International journal of molecular sciences · 2023Review
- Breast Cancer Stem Cells: Signaling Pathways, Cellular Interactions, and Therapeutic Implications.Cancers · 2022Review
- p73α1, a p73 C-terminal isoform, regulates tumor suppression and the inflammatory response via Notch1.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Nuclear and Membrane Receptors for Sex Steroids Are Involved in the Regulation of Delta/Serrate/LAG-2 Proteins in Rodent Sertoli Cells.International journal of molecular sciences · 2022Article
- Circulating Tumor Cells in Breast Cancer Patients: A Balancing Act between Stemness, EMT Features and DNA Damage Responses.Cancers · 2022Review
- Dissecting Tumor Growth: The Role of Cancer Stem Cells in Drug Resistance and Recurrence.Cancers · 2022Review
- Beyond the Double-Strand Breaks: The Role of DNA Repair Proteins in Cancer Stem-Cell Regulation.Cancers · 2021Review
- Mammary Development and Breast Cancer: a Notch Perspective.Journal of mammary gland biology and neoplasia · 2021Review
- Utilizing the Hippo pathway as a therapeutic target for combating endocrine-resistant breast cancer.Cancer cell international · 2021Review
- Celastrol and Triptolide Suppress Stemness in Triple Negative Breast Cancer: Notch as a Therapeutic Target for Stem Cells.Biomedicines · 2021Article
- Cancer stem cells: Culprits in endocrine resistance and racial disparities in breast cancer outcomes.Cancer letters · 2021Article
- Unlocking the Secrets of Cancer Stem Cells with γ-Secretase Inhibitors: A Novel Anticancer Strategy.Molecules (Basel, Switzerland) · 2021Review
- Nuclear Mechanisms Involved in Endocrine Resistance.Frontiers in oncology · 2021Review
- Not all cancers are created equal: Tissue specificity in cancer genes and pathways.Current opinion in cell biology · 2020Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Here, we show for the first time, that the familial breast/ovarian cancer susceptibility gene BRCA1 activates the Notch pathway in breast cells by transcriptional upregulation of Notch ligands and receptors in both normal and cancer cells. We demonstrate through chromatin immunoprecipitation assays that BRCA1 is localized to a conserved intronic enhancer region within the Notch ligand Jagged-1 (JAG1) gene, an event requiring ΔNp63. We propose that this BRCA1/ΔNp63-mediated induction of JAG1 may be important the regulation of breast stem/precursor cells, as knockdown of all three proteins resulted in increased tumoursphere growth and increased activity of stem cell markers such as Aldehyde Dehydrogenase 1 (ALDH1). Knockdown of Notch1 and JAG1 phenocopied BRCA1 knockdown resulting in the loss of Estrogen Receptor-α (ER-α) expression and other luminal markers. A Notch mimetic peptide could activate an ER-α promoter reporter in a BRCA1-dependent manner, whereas Notch inhibition using a γ-secretase inhibitor reversed this process. We demonstrate that inhibition of Notch signalling resulted in decreased sensitivity to the anti-estrogen drug Tamoxifen but increased expression of markers associated with basal-like breast cancer. Together, these findings suggest that BRCA1 transcriptional upregulation of Notch signalling is a key event in the normal differentiation process in breast tissue.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.