Understanding the mechanisms of androgen regulation in the prostate gland is important, because the prostate is affected by several different diseases, in particular prostate cancer. Several ways exist to treat prostate cancer and promote cell cycle arrest and/or epithelial cell death. Treatments involving androgen manipulation include surgical castration, antiandrogens, or substances that inhibit androgen synthesis. 17b-estradiol exerts anti-androgen effects by blocking the hypothalamic production of gonadotropinreleasing hormone and thereby inhibiting the production of testosterone by the testes, but also acts locally via interactions with either of the estrogen receptors found in the gland. The two major drawbacks to the use of antiandrogens or androgen deprivation therapies are the systemic side effects, including physiological and behavioral changes on the one hand, and progression to castration-resistant prostate cancer, which is more aggressive than the original disease, on the other. Although androgens are highly important for prostate cancer development, after androgen deprivation the disease progresses to a castration-resistant state that may be driven by AR mutations, amplifications and/or ligand-independent activation, which can keep the prostate epithelial cells alive in an androgen-poor environment. In addition to the mechanisms centered on AR expression and functioning, a variety of chromosomal and physiological changes are associated with PCa progression, and chromosome aberrations, including frequent bridging. Previous analyses of gene expression revealed significant aspects of prostate physiology. These studies employed different strategies to obtain the data, and arrived at different subsets of genes that are differentially expressed in response to challenging hormonal conditions. Given the extreme drop in secretory function in response to androgen, and the complex interactions between the epithelium and the stroma, it is possible that subtle changes in physiologically important factors are obscured in the mass of information obtained. For instance, Desai et al. pointed out a progressive increase in PTEN expression in the epithelial cells and several genes grouped together to characterize an “immune-inflammatory” response, which was validated and correlated with a high concentration of immune-system cells including macrophages, mast cells and lymphocytes. The concentration of these cells is another complicating component in the analyses of gene expression, because they contribute their own mRNA. Asivartham et al. worked with isolated cells in primary cultures, but in these conditions, the contribution of mutual stromal-epithelial interactions is absent. We therefore hypothesized that a better understanding of the nature of the cells that survive castration would benefit the search for strategies to allow a blockade or at least an extension of the time needed for the transition to the CRPC.