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A high concentration of genistein down-regulates activin A, Smad3 and other TGF-beta pathway genes in human uterine leiomyoma cells
Experimental & Molecular Medicine ; : 281-292, 2012.
Article in English | WPRIM | ID: wpr-186641
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(TM), we identified genes (up- or down-regulated, > or = 1.5 fold, P < or = 0.001), functions and signaling pathways that were altered following treatment with an inhibitory concentration of genistein (50 microg/ml) in UtLM cells. Downregulation of TGF-beta signaling pathway genes, activin A, activin B, Smad3, TGF-beta2 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 down-regulation of activin A and Smad3, both members of the TGF-beta 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.
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Full text: Available Index: WPRIM (Western Pacific) Main subject: Uterine Neoplasms / Signal Transduction / Down-Regulation / Up-Regulation / Transforming Growth Factor beta / Anticarcinogenic Agents / Genistein / Oligonucleotide Array Sequence Analysis / Activins / Cell Line, Tumor Type of study: Prognostic study Limits: Female / Humans Language: English Journal: Experimental & Molecular Medicine Year: 2012 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Uterine Neoplasms / Signal Transduction / Down-Regulation / Up-Regulation / Transforming Growth Factor beta / Anticarcinogenic Agents / Genistein / Oligonucleotide Array Sequence Analysis / Activins / Cell Line, Tumor Type of study: Prognostic study Limits: Female / Humans Language: English Journal: Experimental & Molecular Medicine Year: 2012 Type: Article