Objectives: Androgen receptor (AR) action in benign and malignant tissue is potentiated by a number of co-regulatory proteins that may interact with one or more receptor domains. With improvement of research methodologies, it became possible to detect a number of co-activators whose expression is increased in prostate cancer tissue.
Methods: Manuscripts describing prostate cancer-relevant regulation of cellular events by co-activators are selected and summarized.
Results: AR co-activators may regulate histone modification, proteasomal degradation, chaperones, sumoylation, chromatin remodeling, and cytoskeleton. Some of them (TIF-2) are up-regulated by androgens, whereas the expression of others increases during androgen ablation (p300, CBP, and Tip60). Most co-factors are important for the stimulation of cellular proliferation, although in some cases (ART-27), they act as tumor suppressors and are deleted in prostate cancer tissue. In addition to stimulating AR, some co-activators suppress apoptosis in prostate cancer cells that do not express the AR (p300 and SRC-3). It was recently shown that the inhibition of p300 slows down proliferation, stimulates apoptosis, and inhibits migration and invasion.
Conclusions: Co-factors whose down-regulation results in the alterations of multiple cellular functions may be valid targets for novel therapies in advanced prostate cancer.