T877A-AR agonist and antagonist experimental treatments were generated

Further ontological function classification is based on this interaction network map, by discerning significant clusters of interacting proteins based on the number of protein-protein interaction connections. Of the eight hormone Scutellarein stimulation Oleandrin T877A-AR protein lists, we then systemically applied hierarchal clustering analysis to the experimental conditions. Hierarchical clustering heat-maps representing the grouping of between whole T877A-AR agonist and antagonist experimental treatments were then generated. Between the different experimental conditions, a comparative network analysis was applied, and although four different androgens were used, the proteomic profiles of these androgen ligands do not segregate together, and we observed that progesterone and dexamethasone AR complexes have proteomic profiles that look like R1881 and MB, respectively. Moreover, the protein interaction complex for AR-estradiol-stimulated complexes was most similar to the AR-DHT response interactome. We also proceeded to characterize the gene expression patterns of the multi-panel hormone stimulated LNCaP cells. Analysis of most variably expressed genes between the hormone conditions gave a hierarchical clustering pattern that was much different to the T877A-AR protein-interaction profile. Quite clearly, we again observed that the different androgens used in these stimulation profiles do not segregate together, and that synthetic androgens, like R1881 and MB, do not have the same AR-stimulated transactivation profiles as the natural ligands like testosterone and DHT. Moreover, the functional ontological properties between protein-interaction vs. gene expression profiles of our differential ligand stimulated cells also appear to be very different. Discerning the impact on disease progression from these profiles was of particular interest. To establish statistically significant biological functions, we implemented the incorporation of pathways terms using DAVID. Using the protein interaction data from all the ligand stimulation conditions, the major ontological functions are: RNA pol II dependent transcription, protein biosynthesis, with components of the translational machinery, RNA metabolism,DNA repair, and the proteasome/ubiquitination pathways.

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