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

N. Fortunati , S. Bertino (1) , L. Costantino (1) , M. de Bortoli (2, 3) , A. Compagnone (4) , A. Bandino (1) , M.G. Catalano (1) , G. Boccuzzi (1)

1 Department Clinical Physiopathology
2 Department of Oncological Sciences
3 UNITO - Università degli studi di Torino = University of Turin
4 Biochemistry Section

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 anti-estrogen therapy.

Mots clés: Breast cancer; ERα; HDI; VPA; Antiestrogen

N. Fortunati, S. Bertino, L. Costantino, M. de Bortoli, A. Compagnone, et al.. Valproic acid restores erα and antiestrogen sensitivity to erα-negative breast cancer cells. Molecular and Cellular Endocrinology, 2009, 314 (1), pp.17. ⟨10.1016/j.mce.2009.09.011⟩. ⟨hal-00529011⟩