ArticleCancer research2013
Nitric oxide-dependent downregulation of BRCA1 expression promotes genetic instability.
Article in Cancer research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 41 citations in OpenAlex.
- OFD1 inhibition induces BRCAness to create a therapeutic vulnerability to PARP inhibition in pancreatic cancer.Nature communications · 2025Article
- Oxidative Stress in Breast Cancer: A Biochemical Map of Reactive Oxygen Species Production.Current issues in molecular biology · 2024Review
- Application of nano-radiosensitizers in combination cancer therapy.Bioengineering & translational medicine · 2023Review
- PARP inhibitors in the treatment of ARID1A mutant ovarian clear cell cancer: PI3K/Akt1-dependent mechanism of synthetic lethality.Frontiers in oncology · 2023Article
- The Breast Cancer Protooncogenes HER2, BRCA1 and BRCA2 and Their Regulation by the iNOS/NOS2 Axis.Antioxidants (Basel, Switzerland) · 2022Review
- NOS2 andProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Regulation of Cardiac PKA Signaling by cAMP and Oxidants.Antioxidants (Basel, Switzerland) · 2021Review
- The Role of Nitric Oxide in Cancer: Master Regulator or NOt?International journal of molecular sciences · 2020Review
- Redox inhibition of protein phosphatase PP2A: Potential implications in oncogenesis and its progression.Redox biology · 2019Review
- Nitric oxide-donor/PARP-inhibitor combination: A new approach for sensitization to ionizing radiation.Redox biology · 2019Article
- DYRK1A regulates the recruitment of 53BP1 to the sites of DNA damage in part through interaction with RNF169.Cell cycle (Georgetown, Tex.) · 2019Article
- Radiation-Induced Normal Tissue Damage: Oxidative Stress and Epigenetic Mechanisms.Oxidative medicine and cellular longevity · 2019Review
- Targeted and Off-Target (Bystander and Abscopal) Effects of Radiation Therapy: Redox Mechanisms and Risk/Benefit Analysis.Antioxidants & redox signaling · 2018Review
- Reduction-oxidation (redox) system in radiation-induced normal tissue injury: molecular mechanisms and implications in radiation therapeutics.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2018Review
- Breast cancer pulmonary metastasis is increased in mice undertaking spontaneous physical training in the running wheel; a call for revising beneficial effects of exercise on cancer progression.American journal of cancer research · 2017Article
- Bystander effects of nitric oxide in anti-tumor photodynamic therapy.Cancer cell & microenvironment · 2017Article
- Article
- Role of nitric oxide in the radiation-induced bystander effect.Redox biology · 2015Review
- The dual role of iNOS in cancer.Redox biology · 2015Review
- The Role of Nitric Oxide Synthase Uncoupling in Tumor Progression.Molecular cancer research : MCR · 2015Article
Corrections and comments
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Authors and funding
1 author at 1 institution in 1 country.
Funding
Abstract
Elevated levels of nitric oxide (NO) and reactive nitrogen species (RNS) may link inflammation to the initiation, promotion, and progression of cancer. Traditionally, this link has been thought to be mediated by the effects of NO/RNS in generating DNA damage. However, this damage also stimulates DNA repair responses with subsequent blocks to cell proliferation and apoptosis, thereby preventing accumulation of NO/RNS-generated mutations. In addressing this conundrum, I describe here an alternative mechanism for understanding mutagenesis by NO/RNS. Moderate NO/RNS concentrations stimulated mutagenesis not directly by generating DNA damage but indirectly by modifying the activities of DNA repair and genome stability factors without affecting cell proliferation. NO/RNS at concentrations physiologically relevant to inflammation stimulated PP2A activity, leading to dephosphorylation of RBL2, its accumulation in the nucleus, and formation of RBL2/E2F4 complexes. RBL2/E2F4 formation in turn led to a shift in BRCA1 promoter occupancy from complexes containing activator E2F1 to complexes containing repressor E2F4, downregulating BRCA1 expression. By inhibiting BRCA1 expression, NO/RNS thereby reduces the ability of cells to repair DNA double-strand breaks through homologous recombination repair, increasing the involvement of error-prone nonhomologous end joining (NHEJ). In summary, NO/RNS stimulates genetic instability by inhibiting BRCA1 expression and shifting DNA repair from high fidelity to error-prone mechanisms.
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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.