Activation of estrogen receptor-α by the anion nitrite
Open accessAbstract
In this study, the ability of nitrite and nitrate to mimic the effects of estradiol on growth and gene expression was measured in the human breast cancer cell line MCF-7. Similar to estradiol, treatment of MCF-7 cells with either 1 mumol/L nitrite or 1 mumol/L nitrate resulted in approximately 4-fold increase in cell growth and 2.3-fold to 3-fold increase in progesterone receptor (PgR), pS2, and cathepsin D mRNAs that were blocked by the antiestrogen ICI 182,780. The anions also recruited estrogen receptor-alpha (ERalpha) to the pS2 promoter and activated exogenously expressed ERalpha when tested in transient cotransfection assays. To determine whether nitrite or nitrate was the active anion, diphenyleneiodonium was used to inhibit oxidation/reduction reactions in the cell. The ability of diphenyleneiodonium to block the effects of nitrate, but not nitrite, on the induction of PgR mRNA and the activation of exogenously expressed ERalpha suggests that nitrite is the active anion. Concentrations of nitrite, as low as 100 nmol/L, induced a significant increase in PgR mRNA, suggesting that physiologically and environmentally relevant doses of the anion activate ERalpha. Nitrite activated the chimeric receptor Gal-ER containing the DNA-binding domain of GAL-4 and the ligand-binding domain of ERalpha and blocked the binding of estradiol to the receptor, suggesting that the anion activates ERalpha through the ligand-binding domain. Mutational analysis identified the amino acids Cys381, His516, Lys520, Lys529, Asn532, and His547 as important for nitrite activation of the receptor.
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Nitrite supplementation stimulates hsp70 expression and activates the estrogen receptor alpha in a human breast cancer line.
“stimulate of hsp70 expression and activate the estrogen receptor alpha in a human breast cancer line [102].”
From Current perspectives and challenges in understanding the role of nitrite as an integral player in nitric oxide biology and therapy (2011) · cites this paper as [102]
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- Authors
- Veselik, D. J., Divekar, S., Dakshanamurthy, S., Storchan, G. B., Turner, J. M. A., Graham, K. L., Huang, L., Stoica, A., & Martin, M. B.
- Affiliations
- 1Biochemistry and Molecular and Cellular Biology, Departments of
- 2Oncology, and
- Georgetown University (US)
- Venue
- Cancer Research
- Published
- 2008-05-15
- Volume
- 68
- Issue
- 10
- Pages
- 3950-3958
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- PMC
- PMC3676890
- OpenAlex
- W2146393174
- Cited by
- 42
- References
- 48
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 5 · 2023: 3 · 2022: 1 · 2021: 2 · 2020: 2 · 2019: 1 · 2018: 2 · 2017: 4 · 2016: 4 · 2015: 1 · 2014: 1 · 2013: 2 · 2012: 2
- FWCI
- 1.90
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (CA51008)
- National Cancer Institute (P30 CA-51008, P50-CA-58185, CA-51008, U54CA100970, P50CA058185, U54 CA0100970, P30CA051008)
- National Institute of Environmental Health Sciences (ES 11745, R01ES011745)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- nitrite, nitrate, estrogen receptor alpha, estrogen receptor activation, breast cancer, MCF-7 cells, progesterone receptor, pS2 gene expression, cathepsin D, fulvestrant, diphenyleneiodonium, ligand-binding domain, estradiol binding
- MeSH terms
- Fulvestrant, Amino Acids, Animals, Anions, Cathepsin D, Chlorocebus aethiops, Estradiol, Humans, Molecular Conformation, Nitrites, Promoter Regions, Genetic, Receptors, Progesterone, Transfection, COS Cells, Cell Line, Tumor, Estrogen Receptor alpha
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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