Valproic acid restores erα and antiestrogen sensitivity to erα-negative breast cancer cells
In: ISSN: 0303-7207, 2009
Online
academicJournal
Zugriff:
International audience ; 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.
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Valproic acid restores erα and antiestrogen sensitivity to erα-negative breast cancer cells
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Autor/in / Beteiligte Person: | Fortunati, N. ; Bertino, S. ; Costantino, L. ; De Bortoli, M. ; Compagnone, A. ; Bandino, A. ; Catalano, M.G. ; Boccuzzi, G. ; Department Clinical Physiopathology ; Università degli studi di Torino (UNITO) ; Department of Oncological Sciences ; Section, Biochemistry |
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Zeitschrift: | ISSN: 0303-7207, 2009 |
Veröffentlichung: | HAL CCSD ; Elsevier, 2009 |
Medientyp: | academicJournal |
DOI: | 10.1016/j.mce.2009.09.011 |
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