Ied a regulon consisting of 162 transcripts as a set of transcriptional targets whose expression is affected by HDAC6 activity (Fig. 4a). GO term enrichment analysis (DAVID) confirmed that this list was enriched in genes involved in canonical HDAC6 functions, which include response toPutcha et al. Breast Cancer Study (2015) 17:Web page 9 ofFig. three (See legend on next web page.)Putcha et al. Breast Cancer Investigation (2015) 17:Page ten of(See figure on previous page.) Fig. 3 Compact molecule inhibitors of histone deacetylase 6 (HDAC6) as anticancer approach in inflammatory (IBC). a Normalized numbers of cells when cultures are treated with diverse concentrations of Ricolinostat for two doubling times. b Induction of apoptosis as measured by Annexin-V7-AAD assay in cells shown in a. c Development of IBC cells grown as xenograft models treated with Ricolinostat (50 mgkg once everyday 
for five days per week). Treating with paclitaxel (ten mgkg twice a week) was also incorporated for comparison of the anticancer response. The remedy regimen is graphically shown. Red arrows in every growth curve represent the initiation in the treatments. d Biochemical selectivity profiles in the second generation HDAC6 inhibitors (left table), their efficacy to induce accumulation of Ac–tubulin when IBC and non-IBC cells had been treated at 2.five M for 16 hours (left panel), and because the impact that treating those cells for 1 doubling time had on cell quantity. In all panels asterisks indicate statistically significant variations (t test, p 0.05) for treatment options depending on HDAC6 inhibitors: n =6 for both in vitro and in vivo treatmentsFig. 4 Histone deacetylase six (HDAC6) activity is larger in principal inflammatory breast cancer (IBC) than in non-IBC. a Identification from the regulon controlled by HDAC6. The table shows the GO terms associated with the 162 transcripts of the HDAC6 regulon in breast cancer. b Venn diagrams showing the overlap involving the HDAC6 regulons PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/2129546 obtained from the analysis on the breast cancer (BRCA), colorectal cancer (COAD-READ) and lung adenocarcinoma (LUAD) data sets from the Cancer Genome Atlas (TCGA). c HDAC6 activity score inferred by expression of HDAC6 regulon genes upon treatment with Ricolinostat for 0, 3, 6 and 12 hours (left). Expression change in the HDAC6 regulon network over time upon Ricolinostat therapy at 0 and 12 hours (appropriate): node is color-coded by z-score-transformed expression with red indicating high and blue low expression, and node size is also proportional towards the corresponding expression. Edge is coded by the Pearson correlation of HDAC6 and corresponding regulon node with red indicating positive and blue negative, and also the width is proportional towards the absolute correlation value. d mRNA expression levels (left) and the HDAC6-score (ideal) in key IBC and non-IBC clinical samples. ARACNe reconstruction of gene regulatory networksPutcha et al. Breast Cancer Study (2015) 17:Web page 11 ofunfolded protein-induced strain [180] (Fig. 4a). Interestingly, when we analyzed lung (TCGA LUAD)-specific and colorectal cancer (TCGA COAD-READ)-specific HDAC6 regulons, generated by ARACNe analysis with the corresponding TCGA datasets, we obtained a list of 147 and 138 genes, Glyoxalase I inhibitor (free base) respectively, for which thge overlap using the breast cancer regulon was hugely significant (Fig. 4b). This suggests that the transcriptional footprint in the HDAC6 regulon is highly conserved among epithelial cancer cells. Finally we integrated the expression of all transcripts within the HDAC6 reg.