ArticleProceedings of the National Academy of Sciences of the United States of America2014
Estrogen controls the survival of BRCA1-deficient cells via a PI3K-NRF2-regulated pathway.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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73 citing papers in PubMed, 121 citations in OpenAlex.
- Insights from three decades of BRCA1/2 modeling in mice.Nature genetics · 2026Review
- Oxidative stress and antioxidants in breast cancer: a double-edged sword.Frontiers in oncology · 2026Review
- The NRF2/HO- 1 Pathway: a Potential Regulatory Factor in Fluoride-Induced Colonic Injury under Estrogen Deficiency.Biological trace element research · 2025Article
- Decoding BRCA1 promoter hypermethylation: a new frontier in understanding sporadic breast cancer.Cancer gene therapy · 2025Article
- Article
- Carcinogenic form and characteristics of BRCA pathogenic variant breast cancer.International journal of clinical oncology · 2025Review
- NRF2 deficiency leads to inadequate beta cell adaptation during pregnancy and gestational diabetes.Redox biology · 2025Article
- Thirty Years of BRCA1: Mechanistic Insights and Their Impact on Mutation Carriers.Cancer discovery · 2025Review
- BRCA1 and BRCA2: from cancer susceptibility to synthetic lethality.Genes & development · 2025Review
- [BRCA1 Gene's Mutations And Hereditary Breast Cancer: Genetic, Biological, And Clinical Aspects].Le Mali medical · 2025Review
- The implication of aberrant NRF2 activation in management of female cancers.Frontiers in oncology · 2025Review
- PGK1 Regulates Oxidative Stress in Gestational Diabetes Mellitus through the Estradiol-Keap1-Nrf2 Pathway.International journal of biological sciences · 2025Article
- BRCA1 Promotes Repair of DNA Damage in Cochlear Hair Cells and Prevents Hearing Loss.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Caspase-1-dependent spatiality in triple-negative breast cancer and response to immunotherapy.Nature communications · 2024Article
- Analysis of Expression and Regulation of AKR1C2 in HPV-Positive and -Negative Oropharyngeal Squamous Cell Carcinoma.Cancers · 2024Article
- CGRP as a potential mediator for the sexually dimorphic responses to traumatic brain injury.Biology of sex differences · 2024Article
- Regulation of antioxidants in cancer.Molecular cell · 2024Review
- Kinase signalling adaptation supports dysfunctional mitochondria in disease.Frontiers in molecular biosciences · 2024Review
- The PI3K/Akt-Nrf2 Signaling Pathway and Mitophagy Synergistically Mediate Hydroxytyrosol to Alleviate Intestinal Oxidative Damage.International journal of biological sciences · 2024Article
- Identification of small-molecule inhibitors against the interaction of RNA-binding protein PSF and its target RNA for cancer treatment.PNAS nexus · 2023Article
13 more citing papers are in PubMed but not listed here.
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16 authors at 5 institutions in 2 countries.
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Abstract
Mutations in the tumor suppressor BRCA1 predispose women to breast and ovarian cancers. The mechanism underlying the tissue-specific nature of BRCA1's tumor suppression is obscure. We previously showed that the antioxidant pathway regulated by the transcription factor NRF2 is defective in BRCA1-deficient cells. Reactivation of NRF2 through silencing of its negative regulator KEAP1 permitted the survival of BRCA1-null cells. Here we show that estrogen (E2) increases the expression of NRF2-dependent antioxidant genes in various E2-responsive cell types. Like NRF2 accumulation triggered by oxidative stress, E2-induced NRF2 accumulation depends on phosphatidylinositol 3-kinase-AKT activation. Pretreatment of mammary epithelial cells (MECs) with the phosphatidylinositol 3-kinase inhibitor BKM120 abolishes the capacity of E2 to increase NRF2 protein and transcriptional activity. In vivo the survival defect of BRCA1-deficient MECs is rescued by the rise in E2 levels associated with pregnancy. Furthermore, exogenous E2 administration stimulates the growth of BRCA1-deficient mammary tumors in the fat pads of male mice. Our work elucidates the basis of the tissue specificity of BRCA1-related tumor predisposition, and explains why oophorectomy significantly reduces breast cancer risk and recurrence in women carrying BRCA1 mutations.
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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.