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- Title
ERα and ERβ expression and transcriptional activity are differentially regulated by HDAC inhibitors.
- Authors
Duong, V; Licznar, A; Margueron, R; Boulle, N; Busson, M; Lacroix, M; Katzenellenbogen, B S; Cavaillès, V; Lazennec, G
- Abstract
The proliferative action of ERα largely accounts for the carcinogenic activity of estrogens. By contrast, recent data show that ERβ 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 ERβ protein levels, whereas it decreased ERα 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 ERβ more strongly than that of ERα. 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 ERβ 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 ERβ and HDAC on the control of transcription and cell proliferation constitute a promising approach for cancer therapy.Oncogene (2006) 25, 1799–1806. doi:10.1038/sj.onc.1209102; published online 12 September 2005
- Subjects
ESTROGEN; CELL proliferation; HISTONE deacetylase; TUMOR suppressor genes; GENE expression; CANCER treatment
- Publication
Oncogene, 2006, Vol 25, Issue 12, p1799
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1209102