The role of the androgen receptor in prostate cancer.

Abstract

Androgens are important not only for the development and function of the normal prostate gland, but also for the maintenance of prostate cancer (PCa) cells. The biological function of androgens is exerted by activation of the transcriptional activity of the androgen receptor (AR). The function of the AR in the prostate is largely dependent on AR protein levels and structural integrity of the protein and other transcription activation factors. Based upon the clinical findings that androgen ablation therapy-resistant PCa still expresses AR and the androgen-regulated gene, prostate-specific antigen, a concept is developing that the androgen receptor iscritical for androgen-refractory prostate cancer cells. Indeed, because of the alterations detected in the AR gene, many noncognate activators, including estrogen, progesterone, peptide growth factors, and cytokines, are able to induce transactivation of the AR under androgen-depleted conditions. Also, transactivational activity of the AR is often modulated by crosstalk between the AR and other signaling pathways in cancerous prostatic cells. Dysregulation of AR function in prostate cancer results in an abnormal profile of AR-regulated genes, which include cell cycle regulators, transcription factors, and those proteins important for cell survival, lipogenesis, and secretion. Thus in this review we will evaluate the significance of the AR in the development and progression of prostate cancer.