ArticleThe Journal of biological chemistry2012
BRCA2 protein deficiency exaggerates doxorubicin-induced cardiomyocyte apoptosis and cardiac failure.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- BRCA2 variants and cardiovascular disease in a multi-ethnic study.BMC medical genetics · 2012Pooled it
- Commercially available lifestyle modification program: randomized controlled trial addressing heart and bone health in BRCA1/2+ breast cancer survivors after risk-reducing salpingo-oophorectomy.Journal of cancer survivorship : research and practice · 2017Trial
- Impact of CaInternational journal of molecular sciences · 2026Review
- Exploring the Mechanisms of Total Saponins of Black Ginseng and Ginsenoside Rg3 Against Doxorubicin-Induced Cardiotoxicity.Food science & nutrition · 2026Article
- Breast cancer susceptibility gene 2 upregulation alleviated cardiac hypertrophy in angiotensin II-treated mice.Biochemistry and biophysics reports · 2026Article
- Therapeutic Potential of the Deubiquitinase BRCC3 in Attenuating Ischemic Myocardial Injury and Ventricular Remodeling.Research (Washington, D.C.) · 2026Article
- Anthracyclines-induced cardiotoxicity in patients with early breast cancer carrying germline BRCA1/2 mutation: the BRCAN study.The oncologist · 2025Article
- Different Mechanisms in Doxorubicin-Induced Neurotoxicity: Impact of BRCA Mutations.International journal of molecular sciences · 2025Review
- The cardio-oncologic burden of breast cancer: molecular mechanisms and importance of preclinical models.Basic research in cardiology · 2025Review
- Cardiovascular disease risk after breast cancer treatment in patients with a BRCA1/2 pathogenic variant.Breast cancer research and treatment · 2025Article
- Left ventricular global longitudinal strain is worse in BRCA mutation positive breast cancer patients prior to cancer treatment and premature menopause.Breast cancer research and treatment · 2024Article
- Complex Interplay between DNA Damage and Autophagy in Disease and Therapy.Biomolecules · 2024Review
- Article
- Anthracycline-related cardiotoxicity in patients with breast cancer harboring mutational signature of homologous recombination deficiency (HRD).ESMO open · 2024Article
- DNA damage response signaling: A common link between cancer and cardiovascular diseases.Cancer medicine · 2023Review
- Article
- Associations of Plasma Bioactive Adrenomedullin Levels with Cardiovascular Risk Factors inGeburtshilfe und Frauenheilkunde · 2022Article
- Article
- BReast CAncer susceptibility gene 2 deficiency exacerbates oxidized LDL-induced DNA damage and endothelial apoptosis.Physiological reports · 2020Article
- Article
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 3 countries.
Funding
Abstract
The tumor suppressor breast cancer susceptibility gene 2 (BRCA2) plays an important role in the repair of DNA damage, and loss of BRCA2 predisposes carriers to breast and ovarian cancers. Doxorubicin (DOX) remains the cornerstone of chemotherapy in such individuals. However, it is often associated with cardiac failure, which once manifests carries a poor prognosis. Because BRCA2 regulates genome-wide stability and facilitates DNA damage repair, we hypothesized that loss of BRCA2 may increase susceptibility to DOX-induced cardiac failure. To this aim, we generated cardiomyocyte-specific BRCA2 knock-out (CM-BRCA2(-/-)) mice using the Cre-loxP technology and evaluated their basal and post-DOX treatment phenotypes. Although CM-BRCA2(-/-) mice exhibited no basal cardiac phenotype, DOX treatment resulted in markedly greater cardiac dysfunction and mortality in CM-BRCA2(-/-) mice compared with control mice. Apoptosis in left ventricular (LV) sections from CM-BRCA2(-/-) mice compared with that in corresponding sections from wild-type (WT) littermate controls was also significantly enhanced after DOX treatment. Microscopic examination of LV sections from DOX-treated CM-BRCA2(-/-) mice revealed a greater number of DNA double-stranded breaks and the absence of RAD51 focus formation, an essential marker of double-stranded break repair. The levels of p53 and the p53-related proapoptotic proteins p53-up-regulated modulator of apoptosis (PUMA) and Bax were significantly increased in samples from CM-BRCA2(-/-) mice. This corresponded with increased Bax to Bcl-2 ratios and elevated cytochrome c release in the LV sections of DOX-treated CM-BRCA2(-/-) mice. Taken together, these data suggest a critical and previously unrecognized role of BRCA2 as a gatekeeper of DOX-induced cardiomyocyte apoptosis and susceptibility to overt cardiac failure. Pharmacogenomic studies evaluating cardiac function in BRCA2 mutation carriers treated with doxorubicin are encouraged.
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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.