Prostate cancer (PC) is among the most frequent causes of death for cancer in men in western countries. In about 30% of cases, the disease is very aggressive rapidly leading to a metastatic disease. In these cases, prostatectomy is not possible and the patient is usually directed to androgen deprivation therapy (ADT) which is only palliative as a castration resistant PC (CRPC) usually develops within 2-3 years of treatment. At present there are no prognostic markers of PC progression. The role of the androgen receptor (AR) in initiation and development of PC is well established and documented. In particular, it is now recognized that androgens actions are mediated by an integration of classical (genomic) and non-classical (extragenomic) activity of AR. The picture about AR and PC become less clear when CRPC is considered. Indeed, the role of AR in the progression of PC and in CRPC is controversial. Results of studies on the role of AR in the progression of PC in cell lines, xenografts, animal models and even clinical specimens are conflicting reflecting the high heterogeneity of PC. Recent evidence in AR conditional KO in mouse models of PC shows possible contrasting roles of AR depending on its location in the two (epithelial or stromal) compartments of PC. Here, we review this evidence and report preliminary data of a study performed in microdissected areas of epithelia and stromal compartments of human PC.
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