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

35Citations
Citations of this article
31Readers
Mendeley users who have this article in their library.

This article is free to access.

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 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 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 genis-tein 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 down-regulation 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. Copyright © 2012 by the Korean Society for Biochemistry and Molecular Biology.

Cite

CITATION STYLE

APA

Dixon, D., Di, X., Andrews, D. M. K., Tucker, C. J., Yu, L., Moore, A. B., … Xiao, H. (2012). A high concentration of genistein down-regulates activin a, Smad3 and other TGF-β pathway genes in human uterine leiomyoma cells. Experimental and Molecular Medicine, 44(4), 281–292. https://doi.org/10.3858/emm.2012.44.4.024

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free