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Title: A High-dose of genistein down-regulates TGF-beta pathway genes in human uterine leiomyoma cells      
dateReleased:
04-30-2012
description:
High doses of genistein show an inhibitory effect on uterine leiomyoma (UtLM) cell proliferation. Using microarray analysis and Ingenuity Pathways AnalysisTM, 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 ìg/ml) in UtLM cells. Downregulation of TGF-â signaling pathway genes, activin A, activin B, Smad3, TGF-â2 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 reverse transcriptase-polymerase chain reaction 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-â 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. Cells were treated with either genistein (50 μg/ml) (4’, 5, 7-Trihydroxyisoflavone; Sigma Chemical Company, St. Louis, MO, USA) or the vehicle control [0.3% dimethylsulfoxide (DMSO), Sigma] for 24 h. the samples from the flasks that received the same treatment were pooled, then concentrated to > 9 ìg/ìl by Microcon 30 columns (Amicon:Millipore, Bedford, MA, USA). Three replicates for the treatment, and one pooled control, were submitted for microarray analysis. Gene expression analysis was conducted using Agilent Whole Human Genome arrays (Agilent Technologies, Palo Alto, CA, USA).
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-19477
refinement:
raw
alternateIdentifiers:
19477
keywords:
functional genomics
dateModified:
05-01-2014
availability:
available
types:
gene expression
name:
Homo sapiens
ID:
A-AGIL-11
name:
Agilent Whole Human Genome Oligo Microarray 012391 G4112A
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-19477/E-GEOD-19477.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-19477/E-GEOD-19477.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE19477
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress
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