Evidence map›Paper›PMID 22228119›Full record

ArticleExperimental & molecular medicine2012

A high concentration of genistein down-regulates activin A, Smad3 and other TGF-β pathway genes in human uterine leiomyoma cells.

Xudong Di, Danica M K Andrews, Charles J Tucker, Linda Yu, Alicia B Moore, Xiaolin Zheng, Lysandra Castro, Tonia Hermon, Hang Xiao, Darlene Dixon

Open access · goldAbstract read
In one paragraph

Article in Experimental & molecular medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
3.7field-weighted citation impact, top 8% 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

18 citing papers in PubMed, 36 citations in OpenAlex.

  1. Trial
  2. Review
  3. Article
  4. Review
  5. Review
  6. Review
  7. Article
  8. Recent Advances in Uterine Fibroid Etiology.Seminars in reproductive medicine · 2017
    Review
  9. Article
  10. Dose- and Time-Dependent Transcriptional Response of Ishikawa Cells Exposed to Genistein.Toxicological sciences : an official journal of the Society of Toxicology · 2016
    Article
  11. Article
  12. Review
  13. Review
  14. Article
  15. Transforming growth factor β signaling in uterine development and function.Journal of animal science and biotechnology · 2014
    Review
  16. Article
  17. Article
  18. Article
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

10 authors at 3 institutions in 2 countries.

Xudong DiMolecular Pathogenesis Group, National Toxicology Program (NTP) Laboratories Branch, National Institute of Environmental Health Sciences, National Institutes of Health (NIH), Research Triangle Park, North Carolina 27709, USA.
Danica M K Andrews
Charles J Tucker
Linda Yu
Alicia B Moore
Xiaolin Zheng
Lysandra Castro
Tonia Hermon
Hang Xiao
Darlene Dixon
National Institutes of Health · USNational Institute of Environmental Health Sciences · USNanjing Medical University · CN

Funding

Mammary Gland as a Sensitive End Point to Effects of Endocrine DisruptorsZIAES102785 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI FENTON, SUZANNE · 2010 to 2021
$38.1M
Pathobiology Of Uterine Leiomyomas (fibroids)ZIAES021196 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI DIXON, DARLENE · 2009 to 2025
$31.7M
Gene Expression and MicroarraysZICES102445 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI GERRISH, KEVIN · 2009 to 2025
$31.6M
Stem Cell ToxicologyZIAES102925 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI TOKAR, ERIK · 2010 to 2021
$25.3M
Intramural NIH HHS
6 · The paper itself

Abstract

Previously, we found that high doses of genistein show an inhibitory effect on uterine leiomyoma (UtLM) cell proliferation. In this study, using microarray analysis and Ingenuity Pathways Analysis™, we identified genes (up- or down-regulated, ≥ 1.5 fold, P ≤ 0.001), functions and signaling pathways that were altered following treatment with an inhibitory concentration of genistein (50 μg/ml) in UtLM cells. Downregulation of TGF-β signaling pathway genes, activin A, activin B, Smad3, TGF-β2 and genes related to cell cycle regulation, with the exception of the upregulation of the CDK inhibitor P15, were identified and validated by real- time RT-PCR studies. Western blot analysis further demonstrated decreased protein expression of activin A and Smad3 in genistein-treated UtLM cells. Moreover, we found that activin A stimulated the growth of UtLM cells, and the inhibitory effect of genistein was partially abrogated in the presence of activin A. Overexpression of activin A and Smad3 were found in tissue samples of leiomyoma compared to matched myometrium, supporting the contribution of activin A and Smad3 in promoting the growth of UtLM cells. Taken together, these results suggest that downregulation of activin A and Smad3, both members of the TGF-β pathway, may offer a mechanistic explanation for the inhibitory effect of a high-dose of genistein on UtLM cells, and might be potential therapeutic targets for treatment of clinical cases of uterine leiomyomas.

Indexed as

ActivinsAnticarcinogenic AgentsCell Line, TumorCell ProliferationCyclin-Dependent Kinase Inhibitor p15Down-RegulationFemaleGenisteinHumansLeiomyomaOligonucleotide Array Sequence AnalysisSignal TransductionSmad3 ProteinTransforming Growth Factor betaUp-RegulationUterine Neoplasmsactivin Aactivin BActivinsAnticarcinogenic AgentsCyclin-Dependent Kinase Inhibitor p15GenisteinSmad3 ProteinSMAD3 protein, humanTransforming Growth Factor beta

Identifiers

PMID22228119
PMCPMC3349910
OpenAlexW1967105259

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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.