Evidence map›Paper›PMID 33818655›Full record

ArticleArchives of toxicology2021

"Metalloestrogenic" effects of cadmium downstream of G protein-coupled estrogen receptor and mitogen-activated protein kinase pathways in human uterine fibroid cells.

Linda Yu, Jingli Liu, Yitang Yan, Alanna Burwell, Lysandra Castro, Min Shi, Darlene Dixon

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Archives of toxicology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
0.6field-weighted citation impact, top 36% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.

  1. Pooled it
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  3. Review
  4. Article
  5. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Linda YuMolecular Pathogenesis Group, Mechanistic Toxicology Branch, Division of the National Toxicology Program (DNTP), National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), MDB3-06/B341, 111 T.W. Alexander Drive, Bldg.101, South Campus, P.O. Box 12233, Research Triangle Park, NC, 27709, USA.
Jingli LiuMolecular Pathogenesis Group, Mechanistic Toxicology Branch, Division of the National Toxicology Program (DNTP), National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), MDB3-06/B341, 111 T.W. Alexander Drive, Bldg.101, South Campus, P.O. Box 12233, Research Triangle Park, NC, 27709, USA.
Yitang YanMolecular Pathogenesis Group, Mechanistic Toxicology Branch, Division of the National Toxicology Program (DNTP), National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), MDB3-06/B341, 111 T.W. Alexander Drive, Bldg.101, South Campus, P.O. Box 12233, Research Triangle Park, NC, 27709, USA.
Alanna BurwellMolecular Pathogenesis Group, Mechanistic Toxicology Branch, Division of the National Toxicology Program (DNTP), National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), MDB3-06/B341, 111 T.W. Alexander Drive, Bldg.101, South Campus, P.O. Box 12233, Research Triangle Park, NC, 27709, USA.
Lysandra CastroMolecular Pathogenesis Group, Mechanistic Toxicology Branch, Division of the National Toxicology Program (DNTP), National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), MDB3-06/B341, 111 T.W. Alexander Drive, Bldg.101, South Campus, P.O. Box 12233, Research Triangle Park, NC, 27709, USA.
Min ShiBiostatistics and Computational Biology Branch, Division of the Intramural Program (DIR), National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), Research Triangle Park, NC, 27709, USA.
Darlene DixonMolecular Pathogenesis Group, Mechanistic Toxicology Branch, Division of the National Toxicology Program (DNTP), National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), MDB3-06/B341, 111 T.W. Alexander Drive, Bldg.101, South Campus, P.O. Box 12233, Research Triangle Park, NC, 27709, USA. dixon@niehs.nih.gov.ORCID http://orcid.org/0000-0002-7001-2985
National Institutes of Health · US

Funding

Pathobiology Of Uterine Leiomyomas (fibroids)ZIAES021196 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI DIXON, DARLENE · 2009 to 2025
$31.7M
PATHOBIOLOGY OF UTERINE LEIOMYOMAS (FIBROIDS)Z01ES021196 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI DIXON, DARLENE · 1994 to 2008
$3.9M
Intramural NIH HHS Z01 ES021196
6 · The paper itself

Abstract

Cadmium (Cd) is a toxic metal reported to act as an estrogen "mimic" in the rat uterus and in vitro. We have reported that Cd stimulates proliferation of estrogen-responsive human uterine leiomyoma (ht-UtLM; fibroid) cells through nongenomic signaling involving the G protein-coupled estrogen receptor (GPER), with activation of epidermal growth factor receptor (EGFR) and mitogen-activated protein kinase (pMAPK44/42). In this study, we explored Cd-induced mechanisms downstream of MAPK and whether Cd could stimulate phosphorylation of Histone H3 at serine 10 (H3Ser10ph) through activated Aurora B kinase (pAurora B), a kinase important in activation of histone H3 at serine 10 during mitosis, and if this occurs via Fork head box M1 (FOXM1) and cyclin D1 immediately downstream of MAPK. We found that Cd increased proliferating cell nuclear antigen (PCNA) and H3Ser10ph expression by immunofluorescence, and that H3ser10ph and pAurora B were coexpressed along the metaphase plate in ht-UtLM cells. In addition, Cd-exposed cells showed higher expression of pMAPK44/42, FOXM1, pAurora B, H3ser10ph, and Cyclin D1 by western blotting. Immunoprecipitation and proximity ligation assays further indicated an association between FOXM1 and Cyclin D1 in Cd-exposed cells. These effects were attenuated by MAPK kinase (MEK1/2) inhibitor. In summary, Cd-induced proliferation of ht-UtLM cells occurred through activation of Histone H3 and Aurora B via FOXM1/Cyclin D1 interactions downstream of MAPK. This provides a molecular mechanism of how Cd acts as an "estrogen mimic" resulting in mitosis in hormonally responsive cells.

Indexed as

Aurora Kinase BCadmiumCell ProliferationCells, CulturedCyclin D1FemaleForkhead Box Protein M1HistonesHumansLeiomyomaMitogen-Activated Protein KinasesMitosisReceptors, EstrogenReceptors, G-Protein-CoupledSignal TransductionUterine NeoplasmsAURKB protein, humanAurora Kinase BCadmiumCCND1 protein, humanCyclin D1Forkhead Box Protein M1FOXM1 protein, humanGPER1 protein, humanHistonesMitogen-Activated Protein KinasesReceptors, EstrogenReceptors, G-Protein-CoupledAurora BCyclin D1Fibroid cellsFOXM1H3Ser10ph

Identifiers

PMID33818655
PMCPMC8166678
OpenAlexW3141770151

What Socratic holds

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LicenceCC BY
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Registered trials

None linked

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 Socratic graph.