Figure 2: Newly expressed ERα in prostate cancer cells that disseminate to bone metastasis may reactivate proliferation due to modified AR function through changes in coactivator/corepressor recruitment in the presence of low circulating androgens. Prostate cancer cells alter the bone homeostasis by secreting paracrine factors that regulate proliferation and osteoblast differentiation. These factors include bone morphogenetic protein (BMP), transforming growth factor beta (TGFβ), insulin-like growth factor (IGF), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), endothelin-1, bone metastasis-related factor (MDA-BF-1), plasminogen activator (µPA) and prostate specific antigen (PSA). These growth factors modulate the function of osteoblasts to promote the deposition of a new extracellular matrix and consequently osteoclast activation that induces bone remodeling of low mechanical strength.