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.
CITATION STYLE
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
Mendeley helps you to discover research relevant for your work.