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Epigenetic Modifications with DZNep, NaBu and SAHA in Luminal and Mesenchymal-like Breast Cancer Subtype Cells

2016    Dagdemir, Aslihan; Judes, Gaelle; Lebert, Andre; Echegut, Maureen; Karsli-Ceppioglu, Seher; Rifai, Khaldoun; Daures, Marine; Ngollo, Marjolaine; Dubois, Lucas; Penault-Llorca, Frederique; Bignon, Yves-Jean; Bernard-Gallon, Dominique

Background/Aim: Numerous studies have shown that breast cancer and epigenetic mechanisms have a very powerful interactive relation. The MCF7 cell line, representative of luminal subtype and the MDA-MB 231 cell line representative of mesenchymal-like subtype were treated respectively with a Histone Methyl Transferase Inhibitors (HMTi), 3-Deazaneplanocin hydrochloride (DZNep), two histone deacetylase inhibitors (HDACi), sodium butyrate (NaBu), and suberoylanilide hydroxamic acid (SAHA) for 48 h. Materials and Methods: Chromatin immunoprecipitation (ChIP) was used to observe HDACis (SAHA and NaBu) and HMTi (DZNep) impact on histones and more specifically on H3K27me3, H3K9ac and H3K4ac marks with Q-PCR analysis of BRCA1, SRC3 and P300 genes. Furthermore, the HDACi and HMTi effects on mRNA and protein expression of BRCA1, SRC3 and P300 genes were checked. In addition, statistical analyses were used. Results: In the MCF7 luminal subtype with positive ER, H3k4ac was significantly increased on BRCA1 with SAHA. On the contrary, in the MDA-MB 231 breast cancer cell line, representative of mesenchymal-like subtype with negative estrogen receptor, HDACis had no effect. Also, DZNEP decreased significantly H3K27me3 on BRCA1 in MDA-MB 231. Besides, on SRC3, a significant increase for H3K4ac was obtained in MCF7 treated with SAHA. And DZNEP had no effect in MCF7. Also, in MDA-MB 231 treated with DZNEP, H3K27me3 significantly decreased on SRC3 while H3K4ac was significantly increased in MDA-MB-231 treated with SAHA or NaBu for P300. Conclusion: Luminal and mesenchymal-like breast cancer subtype cell lines seemed to act differently to HDACis (SAHA and NaBu) or HMTi (DZNEP) treatments.