| Added by | mollevi |
|---|---|
| Group name | EquipeMY |
| Item Type | Journal Article |
| Title | Histone deacetylase 9 regulates breast cancer cell proliferation and the response to histone deacetylase inhibitors |
| Creator | Lapierre et al. |
| Author | Marion Lapierre |
| Author | Aurélien Linares |
| Author | Mathieu Dalvai |
| Author | Céline Duraffourd |
| Author | Sandrine Bonnet |
| Author | Abdelhay Boulahtouf |
| Author | Carmen Rodriguez |
| Author | Stéphan Jalaguier |
| Author | Said Assou |
| Author | Patrick Balaguer |
| Author | Thierry Maudelonde |
| Author | Philippe Blache |
| Author | Kerstin Bystricky |
| Author | Nathalie Boulle |
| Author | Vincent Cavaillès |
| Abstract | Histone lysine acetylation is an epigenetic mark regulated by histone acetyltransferases and histone deacetylases (HDAC) which plays an important role in tumorigenesis. In this study, we observed a strong overexpression of class IIa HDAC9, at the mRNA and protein levels, in the most aggressive human breast cancer cell lines (i.e. in basal breast cancer cells vs luminal ones or in malignant vs begnin MCF10A breast epithelial cell lines). HDAC9 overexpression was associated with higher rates of gene transcription and increased epigenetic marks on the HDAC9 promoter. Ectopic expression of HDAC9 in MCF7 luminal breast cancer cells led to an increase in cell proliferation and to a decrease in apoptosis. These effects were associated with a deregulated expression of several genes controlled by HDAC inhibitors such as CDKN1A, BAX and TNFRSF10A. Inversely, knock-down of HDAC9 expression in MDA-MB436 basal breast cancer cells reduced cell proliferation. Moreover, high HDAC9 expression decreased the efficacy of HDAC inhibitors to reduce cell proliferation and to regulate CDKN1A gene expression. Interestingly, the gene encoding the transcription factor SOX9 was identified by a global transcriptomic approach as an HDAC9 target gene. In stably transfected MCF7 cells, SOX9 silencing significantly decreased HDAC9 mitogenic activity. Finally, in a large panel of breast cancer biopsies, HDAC9 expression was significantly increased in tumors of the basal subtype, correlated with SOX9 expression and associated with poor prognosis. Altogether, these results indicate that HDAC9 is a key factor involved in mammary carcinogenesis and in the response to HDAC inhibitors. |
| Publication | Oncotarget |
| Volume | 7 |
| Issue | 15 |
| Pages | 19693-19708 |
| Date | Apr 12, 2016 |
| Journal Abbr | Oncotarget |
| Language | eng |
| DOI | 10.18632/oncotarget.7564 |
| ISSN | 1949-2553 |
| Library Catalog | PubMed |
| Extra | PMID: 26930713 PMCID: PMC4991412 |
| Tags | Apoptosis, Blotting, Western, breast cancer, Breast Neoplasms, Cell Line, Cell Line, Tumor, Cell Proliferation, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, HDAC inhibitors, HDAC9, histone deacetylase, Histone Deacetylase Inhibitors, Histone Deacetylases, Humans, MCF-7 Cells, Microscopy, Fluorescence, original, Repressor Proteins, RNA Interference, SOX9, SOX9 Transcription Factor |
| Date Added | 2018/11/13 - 17:26:05 |
| Date Modified | 2019/05/21 - 14:41:00 |
Institut de Recherche en Cancérologie de
