Androgen Receptors in Prostate Cancer

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Abstract
Androgen receptor (AR) is expressed in the majority of human prostate cancers. For a better understanding of prostate carcinoma events it is necessary to present findings on the regulation of AR target genes, AR interaction with associated proteins, ligand independent activation and point mutations. A comprehensive literature review of manuscripts published on AR in prostate cancer was performed using PubMed. AR regulates the expression of genes involved in the proliferation and differentiation of prostate cancer cells. Due to differential interactions with coactivators and corepressors AR activation results in the stimulation of a mitogenic response or in the expression of secretory proteins. AR is functional in advanced carcinoma of the prostate, as evidenced in studies of mutant receptors and ligand independent activation. AR point mutations appear in advanced prostate cancer more frequently than in organ confined disease. Current therapy options aimed to inhibit AR function in prostate cancer are limited. Antiandrogenic drugs frequently acquire agonistic properties in the presence of mutated ARs. In addition, androgen signaling pathway activity increases during long-term androgen ablation. AR coactivator complexes might be a target for novel therapies for prostate cancer.

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