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题目:: HDAC inhibition does not induce estrogen receptor in human triple-negative breast cancer cell lines and patient-derived xenografts.
作者:: de Cremoux(Patricia),Dalvai(Mathieu),N'Doye(Olivia),Moutahir(Fatima),Rolland(Gaëlle),Chouchane-Mlik(Olfa),Assayag(Franck),Lehmann-Che(Jacqueline),Kraus-Berthie(Laurence),Nicolas(André),Lockhart(Brian Paul),Marangoni(Elisabetta),de Thé(Hugues),Depil(Stéphane),Bystricky(Kerstin),Decaudin(Didier)
状态:: 发布时间2015-01-20 , 更新时间 2015-01-20
期刊:: Breast Cancer Res Treat
摘要:: 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.
语言:: eng
DOI:: 10.1007/s10549-014-3233-y

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