ArticleToxicological sciences : an official journal of the Society of Toxicology2011
Detoxification: a novel function of BRCA1 in tumor suppression?
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 31 citations in OpenAlex.
- An integrated network toxicology and multi-omics framework prioritizes BRCA1 as a testable candidate in benzo[a]pyrene-associated oral cancer.Frontiers in pharmacology · 2026Article
- Carbamate compounds induced toxic effects by affecting Nrf2 signaling pathways.Toxicology reports · 2024Review
- Transcription Factor NRF2 in Shaping Myeloid Cell Differentiation and Function.Advances in experimental medicine and biology · 2024Review
- How to deal with frenemy NRF2: Targeting NRF2 for chemoprevention and cancer therapy.Journal of food and drug analysis · 2023Review
- Oxidative Stress and Cancer Heterogeneity Orchestrate NRF2 Roles Relevant for Therapy Response.Molecules (Basel, Switzerland) · 2022Review
- Impaired antioxidant KEAP1-NRF2 system in amyotrophic lateral sclerosis: NRF2 activation as a potential therapeutic strategy.Molecular neurodegeneration · 2021Review
- Effect of Hepatitis Viruses on the Nrf2/Keap1-Signaling Pathway and Its Impact on Viral Replication and Pathogenesis.International journal of molecular sciences · 2019Review
- Emerging role of nuclear factor erythroid 2-related factor 2 in the mechanism of action and resistance to anticancer therapies.Cancer drug resistance (Alhambra, Calif.) · 2019Review
- Transcriptional Regulation by Nrf2.Antioxidants & redox signaling · 2018Review
- Breast cancer susceptibility protein 1 (BRCA1) rescues neurons from cerebral ischemia/reperfusion injury through NRF2-mediated antioxidant pathway.Redox biology · 2018Article
- Epidermal Growth Factor Receptor Kinase Inhibitors Synergize with TCDD to Induce CYP1A1/1A2 in Human Breast Epithelial MCF10A Cells.Drug metabolism and disposition: the biological fate of chemicals · 2016Article
- Estrogen potentiates reactive oxygen species (ROS) tolerance to initiate carcinogenesis and promote cancer malignant transformation.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Review
- Nrf2 promotes survival following exposure to ionizing radiation.Free radical biology & medicine · 2015Review
- BRCA1 and Oxidative Stress.Cancers · 2014Article
- BRCA1 and estrogen/estrogen receptor in breast cancer: where they interact?International journal of biological sciences · 2014Review
- BRCA1 interacts with Nrf2 to regulate antioxidant signaling and cell survival.The Journal of experimental medicine · 2013Article
- Bioactive food components prevent carcinogenic stress via Nrf2 activation in BRCA1 deficient breast epithelial cells.Toxicology letters · 2012Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Our studies found that BRCA1 levels negatively correlate with DNA adducts induced by Benzo(a)pyrene (BaP). Pulse-chase experiments showed that the increase in BaP-induced DNA adducts in BRCA1 knockdown cells may not be associated with BRCA1's function in nucleotide excision repair activity; rather, it may be associated with its function in modulating transcriptional regulation. BRCA1 knockdown in MCF-10A cells significantly attenuated the induction of CYP1A1 following BaP treatment indicating that the increase in BaP-induced adducts in BRCA1 knockdown cells is not CYP1A1 dependent. However, our study shows that BRCA1 defective cells may still be able to biotransform BaP by regulating other CYP enzymes, including CYP1B1. Knockdown of BRCA1 also severely affected the expression levels of two types of uridine diphosphate glucorunyltransferase (UGT1A1 and UGT1A9) and NRF2. Both UGTs are known as BaP-specific detoxification enzymes, and NRF2 is a master regulator of antioxidant and detoxification genes. Thus, we concluded that the increased amount of BaP-induced DNA adducts in BRCA1 knockdown cells is strongly associated with its loss of functional detoxification. Chromatin immunoprecipitation assay revealed that BRCA1 is recruited to the promoter/enhancer sequences of UGT1A1, UGT1A9, and NRF2. Regulation of UGT1A1 and UGT1A9 expression showed that the induction of DNA adducts by BaP is directly affected by their expression levels. Finally, overexpression of UGTs, NRF2, or ARNT significantly decreased the amount of BaP-induced adducts in BRCA1-deficient cells. Overall, our results suggest that BRCA1 protects cells by reducing the amount of BaP-induced DNA adducts possibly via transcriptional activation of detoxification gene expression.
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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.