Culig Zoran, Klocker Helmut, Bartsch Georg, Steiner Hannes, Hobisch Alfred
Department of Urology, University of Innsbruck, Austria.
J Urol. 2003 Oct;170(4 Pt 1):1363-9. doi: 10.1097/01.ju.0000075099.20662.7f.
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.
雄激素受体（AR）在大多数人类前列腺癌中均有表达。为了更好地理解前列腺癌的发病过程，有必要展示关于AR靶基因调控、AR与相关蛋白相互作用、非配体依赖性激活以及点突变的研究结果。
使用PubMed对已发表的关于前列腺癌中AR的手稿进行全面的文献综述。
AR调节参与前列腺癌细胞增殖和分化的基因表达。由于与共激活因子和共抑制因子的相互作用不同，AR激活会导致有丝分裂反应的刺激或分泌蛋白的表达。AR在晚期前列腺癌中具有功能，这在突变受体和非配体依赖性激活的研究中得到了证实。AR点突变在晚期前列腺癌中比在局限性疾病中更频繁出现。
目前旨在抑制前列腺癌中AR功能的治疗选择有限。抗雄激素药物在存在突变AR时经常获得激动剂特性。此外，在长期雄激素剥夺期间，雄激素信号通路活性增加。AR共激活因子复合物可能是前列腺癌新疗法的靶点。
