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Article Dans Une Revue Oncogene Année : 2006

ERalpha and ERbeta expression and transcriptional activity are differentially regulated by HDAC inhibitors.

Résumé

The proliferative action of ERalpha largely accounts for the carcinogenic activity of estrogens. By contrast, recent data show that ERbeta displays tumor-suppressor properties, thus supporting the interest to identify compounds that could increase its activity. Here, we show that histone deacetylase inhibitors (HDI) upregulated ERbeta protein levels, whereas it decreased ERalpha expression. Part of this regulation took place at the mRNA level through a mechanism independent of de novo protein synthesis. In addition, we found that, in various cancer cells, the treatment with different HDI enhanced the ligand-dependent activity of ERbeta more strongly than that of ERalpha. On the other hand, in MDA-MB231 and HeLa cells, the expression of ERs modified the transcriptional response to HDI. The use of deletion mutants of both receptors demonstrated that AF1 domain of the receptors was required. Finally, we show that ERbeta expression led to a dramatic increased in the antiproliferative activity of HDI, which correlated with a modification of the transcription of genes involved in cell cycle control by HDI. Altogether, these data demonstrate that the interference of ERbeta and HDAC on the control of transcription and cell proliferation constitute a promising approach for cancer therapy.
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Dates et versions

inserm-00143967 , version 1 (30-04-2007)

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Vanessa Duong, Anne Licznar, Raphaël Margueron, Nathalie Boulle, Muriel Busson, et al.. ERalpha and ERbeta expression and transcriptional activity are differentially regulated by HDAC inhibitors.. Oncogene, 2006, 25 (12), pp.1799-806. ⟨10.1038/sj.onc.1209102⟩. ⟨inserm-00143967⟩
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