Evidence map›Paper›PMID 25343777›Full record

ArticleEnvironmental health perspectives2015

Cadmium and proliferation in human uterine leiomyoma cells: evidence of a role for EGFR/MAPK pathways but not classical estrogen receptor pathways.

Xiaohua Gao, Linda Yu, Alicia B Moore, Grace E Kissling, Michael P Waalkes, Darlene Dixon

Open access · diamondAbstract read
In one paragraph

Article in Environmental health perspectives, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

20 citing papers in PubMed, 31 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Mechanisms of Heavy Metal Cadmium (Cd)-Induced Malignancy.Biological trace element research · 2025
    Review
  5. Article
  6. Prolonged cadmium exposure alters benign uterine fibroid cell behavior, extracellular matrix components, and TGFB signaling.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021
    Article
  7. Article
  8. Article
  9. Article
  10. The influence of long-term cadmium exposure on the male advertisement call of Xenopus laevis.Environmental science and pollution research international · 2020
    Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Blood cadmium and volume of uterine fibroids in premenopausal women.Annals of occupational and environmental medicine · 2017
    Article
  17. Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

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5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Xiaohua GaoMolecular Pathogenesis Group, National Toxicology Program (NTP) Laboratory, Division of the NTP (DNTP).
Linda Yu
Alicia B Moore
Grace E Kissling
Michael P Waalkes
Darlene Dixon
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
Statistical collaboration in environmental health researchZIAES103106 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI KISSLING, GRACE E · 2012 to 2017
$656k
Intramural NIH HHS
6 · The paper itself

Abstract

backgroundIt has been proposed that cadmium (Cd) is an environmental "metalloestrogen" and that its action is mediated via the estrogen receptor (ER). Cd mimics the effects of estrogen in the rat uterus, and blood Cd concentrations positively correlate with ER levels in uteri of women with fibroids.

objectivesIn the present study we explored whether Cd could stimulate proliferation of estrogen-responsive human uterine leiomyoma (ht-UtLM) cells and uterine smooth muscle cells (ht-UtSMCs) through classical interactions with ERα and ERβ, or by nongenomic mechanisms.

methodsWe used estrogen response element (ERE) reporters, phosphorylated receptor tyrosine kinase arrays, Western blot analysis, estrogen binding, and cell proliferation assays to evaluate the effects of Cd on ht-UtLM cells and ht-UtSMCs.

resultsCd stimulated growth of both cell types at lower concentrations and inhibited growth at higher concentrations (≥ 50 μM). Cd did not significantly bind to ERα or ERβ, nor did it show transactivation in both cell types transiently transfected with ERE reporter genes. However, in both cells types, Cd (0.1 μM and 10 μM) activated p44/42 MAPK (ERK1/2), and a MAPK inhibitor (PD98059) abrogated Cd-induced cell proliferation. Cd in ht-UtLM cells, but not in ht-UtSMCs, activated the growth factor receptors EGFR, HGFR, and VEGF-R1 upstream of MAPK. Additional studies in ht-UtLM cells showed that AG1478, an EGFR inhibitor, abolished Cd-induced phosphorylation of EGFR and MAPK.

conclusionsOur results show that low concentrations of Cd stimulated cell proliferation in estrogen-responsive uterine cells by nongenomic activation of MAPK, but not through classical ER-mediated pathways.

Indexed as

CadmiumCell Line, TumorCell ProliferationErbB ReceptorsEstrogen Receptor alphaEstrogen Receptor betaFemaleHumansLeiomyomaMitogen-Activated Protein KinasesSignal TransductionUterine NeoplasmsCadmiumErbB ReceptorsEstrogen Receptor alphaEstrogen Receptor betaMitogen-Activated Protein Kinases

Identifiers

PMID25343777
PMCPMC4384203
OpenAlexW2013054227

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Registered trials

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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.