ArticlePloS one2012
Arsenic induces functional re-expression of estrogen receptor α by demethylation of DNA in estrogen receptor-negative human breast cancer.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Breast Cancer and Arsenic Anticancer Effects: Systematic Review of the Experimental Data fromBioMed research international · 2022Pooled it
- Effects of Arsenic Trioxide in MRL/lpr Mice: Disease-Context Support from Human Transcriptomic and DNA Methylation Datasets.Biological trace element research · 2026Article
- The Role of Heavy Metals in the Biology of Female Cancers.International journal of molecular sciences · 2025Review
- c-Myc knockdown restores tamoxifen sensitivity in triple-negative breast cancer by reactivating the expression of ERα: the central role of miR-152 and miR-148a.Breast cancer (Tokyo, Japan) · 2025Article
- Association of urinary cadmium and arsenic with gynecological cancers: Results from NHANES 2003-2018.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Article
- A high-throughput drug screen reveals means to differentiate triple-negative breast cancer.Oncogene · 2022Article
- Anticancer mechanisms of phytochemical compounds: focusing on epigenetic targets.Environmental science and pollution research international · 2021Review
- Resveratrol attenuates arsenic-induced cognitive deficits via modulation of Estrogen-NMDAR-BDNF signalling pathway in female mouse hippocampus.Psychopharmacology · 2021Article
- Premature Menopause, Clonal Hematopoiesis, and Coronary Artery Disease in Postmenopausal Women.Circulation · 2021Article
- Arsenic exposure increased expression of HOTAIR and LincRNA-p21 in vivo and vitro.Environmental science and pollution research international · 2021Article
- Liposome-Coated Arsenic-Manganese Complex for Magnetic Resonance Imaging-Guided Synergistic Therapy Against Carcinoma.International journal of nanomedicine · 2021Article
- Inorganic arsenic influences cell apoptosis by regulating the expression of MEG3 gene.Environmental geochemistry and health · 2021Article
- The human tumor microbiome is composed of tumor type-specific intracellular bacteria.Science (New York, N.Y.) · 2020Article
- Low dosage of arsenic trioxide inhibits vasculogenic mimicry in hepatoblastoma without cell apoptosis.Molecular medicine reports · 2018Article
- Arsenic trioxide increases expression of secreted frizzled-related protein 1 gene and inhibits the WNT/β-catenin signaling pathway in Jurkat cells.Experimental and therapeutic medicine · 2017Article
- Oncogenomic disruptions in arsenic-induced carcinogenesis.Oncotarget · 2017Review
- Oestrogen receptor negativity in breast cancer: a cause or consequence?Bioscience reports · 2016Review
- Epigenetics of breast cancer: Modifying role of environmental and bioactive food compounds.Molecular nutrition & food research · 2016Review
- Vimentin-Mediated Steroidogenesis Induced by Phthalate Esters: Involvement of DNA Demethylation and Nuclear Factor κB.PloS one · 2016Article
- Inhibition of transforming growth factor beta/SMAD signal by MiR-155 is involved in arsenic trioxide-induced anti-angiogenesis in prostate cancer.Cancer science · 2014Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Estrogen receptor α (ERα) is a marker predictive for response of breast cancers to endocrine therapy. About 30% of breast cancers, however, are hormone- independent because of lack of ERα expression. New strategies are needed for re-expression of ERα and sensitization of ER-negative breast cancer cells to selective ER modulators. The present report shows that arsenic trioxide induces reactivated ERα, providing a target for therapy with ER antagonists. Exposure of ER-negative breast cancer cells to arsenic trioxide leads to re-expression of ERα mRNA and functional ERα protein in in vitro and in vivo. Luciferase reporter gene assays and 3-(4,5-dimethylthiazol-2-yl)- 5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assays show that, upon exposure to arsenic trioxide, formerly unresponsive, ER-negative MDA-MB-231 breast cancer cells become responsive to ER antagonists, 4-hydroxytamoxifen and ICI 182,780. Furthermore, methylation- specific PCR and bisulfite-sequencing PCR assays show that arsenic trioxide induces partial demethylation of the ERα promoter. A methyl donor, S-adenosylmethionine (SAM), reduces the degree of arsenic trioxide-induced re-expression of ERα and demethylation. Moreover, Western blot and ChIP assays show that arsenic trioxide represses expression of DNMT1 and DNMT3a along with partial dissociation of DNMT1 from the ERα promoter. Thus, arsenic trioxide exhibits a previously undefined function which induces re-expression ERα in ER-negative breast cancer cells through demethylation of the ERα promoter. These findings could provide important information regarding the application of therapeutic agents targeting epigenetic changes in breast cancers and potential implication of arsenic trioxide as a new drug for the treatment of ER-negative human breast cancer.
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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.