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Article Dans Une Revue Breast Cancer Research and Treatment Année : 2015

HDAC inhibition does not induce estrogen receptor in human triple-negative breast cancer cell lines and patient-derived xenografts

Patricia De Cremoux
  • Fonction : Auteur
Mathieu Dalvai
  • Fonction : Auteur
Olivia N'Doye
  • Fonction : Auteur
Fatima Moutahir
  • Fonction : Auteur
Gaëlle Rolland
  • Fonction : Auteur
Olfa Chouchane-Mlik
  • Fonction : Auteur
Franck Assayag
  • Fonction : Auteur
Jacqueline Lehmann-Che
Laurence Kraus-Berthie
  • Fonction : Auteur
André Nicolas
  • Fonction : Auteur
Brian Paul Lockhart
  • Fonction : Auteur
Elisabetta Marangoni
Stéphane Depil
Kerstin Bystricky
Didier Decaudin
  • Fonction : Auteur

Résumé

Several publications have suggested that histone deacetylase inhibitors (HDACis) could reverse the repression of estrogen receptor alpha (ERα) in triple-negative breast cancer (TNBC) cell lines, leading to the induction of a functional protein. Using different HDACis, vorinostat, panobinostat, and abexinostat, we therefore investigated this hypothesis in various human TNBC cell lines and patient-derived xenografts (PDXs). We used three human TNBC cell lines and three PDXs. We analyzed the in vitro toxicity of the compounds, their effects on the hormone receptors and hormone-related genes and protein expression both in vitro and in vivo models. We then explored intra-tumor histone H3 acetylation under abexinostat in xenograft models. Despite major cytotoxicity of all tested HDAC inhibitors and repression of deactylation-dependent CCND1 gene, neither ERα nor ERβ, ESR1 or ESR2 genes respectively, were re-expressed in vitro. In vivo, after administration of abexinostat for three consecutive days, we did not observe any induction of ESR1 or ESR1-related genes and ERα protein expression by RT-qPCR and immunohistochemical methods in PDXs. This observation was concomitant to the fact that in vivo administration of abexinostat increased intra-tumor histone H3 acetylation. These observations do not allow us to confirm previous studies which suggested that HDACis are able to convert ER-negative (ER-) tumors to ER-positive (ER+) tumors, and that a combination of HDAC inhibitors and hormone therapy could be proposed in the management of TNBC patients.

Domaines

Cancer
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Dates et versions

hal-03653860 , version 1 (28-04-2022)

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Citer

Patricia De Cremoux, Mathieu Dalvai, Olivia N'Doye, Fatima Moutahir, Gaëlle Rolland, et al.. HDAC inhibition does not induce estrogen receptor in human triple-negative breast cancer cell lines and patient-derived xenografts. Breast Cancer Research and Treatment, 2015, 149 (1), pp.81-89. ⟨10.1007/s10549-014-3233-y⟩. ⟨hal-03653860⟩
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