Valproic acid restores ERα and antiestrogen sensitivity to ERα-negative breast cancer cells

Histone deacetylase inhibitors (HDIs) are valuable drugs in breast cancer where estrogen receptor α (ERα) can be silenced by epigenetic modifications. We report the effect of the clinically available HDI, valproic acid (VPA), on ERα expression and function in ER-negative breast cancer cells, MDA-MB-...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Molecular and cellular endocrinology 2010-01, Vol.314 (1), p.17-22
Hauptverfasser: Fortunati, N., Bertino, S., Costantino, L., De Bortoli, M., Compagnone, A., Bandino, A., Catalano, M.G., Boccuzzi, G.
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:Histone deacetylase inhibitors (HDIs) are valuable drugs in breast cancer where estrogen receptor α (ERα) can be silenced by epigenetic modifications. We report the effect of the clinically available HDI, valproic acid (VPA), on ERα expression and function in ER-negative breast cancer cells, MDA-MB-231. VPA induced ERα mRNA and protein, while did not modify ERβ. In VPA-treated cells, we also observed: (1) a correct transcriptional response to estradiol after transfection with the luciferase gene under the control of an estrogen-responsive minimal promoter (ERE-TKluc); (2) increased expression of the ER-related transcription factor FoxA1; (3) estradiol-induced up-regulation of several estrogen-regulated genes (e.g. pS2, progesterone receptor); (4) inhibitory effect of tamoxifen on cell growth. In conclusion, the HDI VPA, inducing ERα and FoxA1, confers to MDA-MB 231 cells an estrogen-sensitive “phenotype”, restoring their sensitivity to antiestrogen therapy.
ISSN:0303-7207
1872-8057
0303-7207
DOI:10.1016/j.mce.2009.09.011