Abstract Title:

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

Abstract Source:

Exp Mol Med. 2012 Jan 6. Epub 2012 Jan 6. PMID: 22228119

Abstract Author(s):

X Di, D M Andrews, C J Tucker, L Yu, A B Moore, X Zheng, L Castro, T Hermon, H Xiao, D Dixon

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 mg/ml) in UtLM cells. Downregulation of TGF-b signaling pathway genes, activin A, activin B, Smad3, TGF-b2 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-b 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.

Study Type : Commentary

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