Characterization of T877A-AR protein interaction and gene expression profiles.

<p><b>A.</b> Quantified protein interaction network of DHT stimulated LNCaP cells. The value of each protein, defined by our label-free quantitative MS, is distinguished by both color and size, and sub-sequent protein-protein interactions. The AR is designated by the black circle. To determine the relationship between protein interaction and gene expression patterns, hierarchical clustering of multi-panel hormone-stimulated LNCaP cells was carried out. <b>B.</b> Interacting proteins identified by mass spectrometry. <b>C.</b> Most variably expressed genes upon ligand stimulation. Although it has been suggested that all hormones used are able to activate androgen-dependent gene transcription with the T877A-AR mutant receptor, there are differences between AR protein complexes and AR gene expression patterns. This cluster analysis illustrates that even the synthetic androgens like Mibolerone (MB) and R1881, have similar gene expression profiles, their protein-interaction complexes are more similar to dexamethasone (DEX) and progesterone (PGR), respectively, than to either natural androgens testosterone and DHT. Moreover, even natural androgens (DHT and testosterone) can be segregated by their protein complexes. This would suggest that there are functions for the AR beyond gene transactivation. Protein and gene expression values are given as a ratio of quantified protein of each stimulation vs. vehicle control stimulation.