The androgen receptor (AR) is a nuclear transcription factor and is composed of four domains: the N-terminal domain (i.e., transcriptional activation domain), DNA-binding domain, a hinge region and the ligand-binding domain (i.e., C-terminal). A simplistic model of canonical AR signaling involves: (1) androgen binding the AR ligand binding domain, (2) dissociation of chaperone proteins (i.e., heat shock proteins), (3) AR nuclear transport and dimerization (likely through microtubule interaction with the hinge region), (4) binding of dimerized AR to androgen response elements (ARE) located within the promoters of AR target genes, (5) recruitment of AR coactivators and (6) transcription of AR target genes. A number of additional events, such as AR phosphorylation and interaction with other coregulators and transcription factors likely also play a role in modulating transcription of AR target genes. The AR represents perhaps the first described lineage-specific oncogene, with prostate cancer demonstrating a persistent addiction to AR signaling even in its late stages, a reflection of its emergence from normal prostatic epithelium. The survival of a given prostate cancer cell is tightly linked to persistent AR signaling, and as such, these malignant cells undergo a number of adaptive changes to ensure persistent AR signaling.
Anti-Human Androgen Receptor (G122-434)-154Sm—100 Tests