Fig. 2

Impact of Dot1L and menin blockade on gene expression and cell functions in BC cells. A Venn diagram showing the number of specific and common transcripts up-regulated (red) and down-regulated (green) following EPZ or MI-2 treatment. B Bar charts from KEGG functional enrichment analysis showing statistically significant common pathways deregulated upon MCF-7 cell treatment with EPZ and MI-2. C Circos plot showing common up-regulated (red) and down-regulated (green) transcripts following EPZ and MI-2 treatment harboring Dot1L + menin binding sites and the statistically significant (p ≤ 0.05) pathways they are involved in. Effect of Dot1L and menin pharmacological blockade on AE-sensitive (MCF7; D) tamoxifen (MCF7 TAM-R; E)- or fulvestrant/ICI (MCF7 ICI-R; F)-resistant BC cells following increasing concentrations of EPZ (up) or MI-136 (bottom) after 3, 6 and 9 days. DMSO was used as control. Data are presented as mean ± SD from six independent replicates. Combenefit software was used to generate dose–response surface curves in AE-sensitive (MCF7; G) tamoxifen (MCF7 TAM-R; H)- or fulvestrant/ICI (MCF7 ICI-R; I)-resistant BC cells, according to D-R Lowe model, combining increasing dose of EPZ and MI-136 for 9 days. Color scale bar indicate the level of synergy (blue) or antagonism (red) at each combination. Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) analysis of ESR1 () mRNA level in AE-sensitive (MCF7; J) tamoxifen (MCF7 TAM-R; K)- or fulvestrant/ICI (MCF7 ICI-R; L)-resistant BC cells following EPZ or MI-136 as single agents and in combination after 9 days of treatment. RT-qPCR results shown are the mean ± SD of triplicate determinations from a representative experiment. Asterisks indicate statistically significant differences (*p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.005) to CTRL or to single treatment (black bars)