Hence, in PTHrP-secreting breast cancers that metastasize to bone, the CaSR initiates a vicious cycle in which PTHrP-induced bone resorption raises the concentration of extracellular Ca2+ and transforming growth factor-β within the bone microenvironment, which then act in concert to evoke further PTHrP release and worsening osteolysis (Sanders et al., 2001). The gene discussed is CASR; the disease is breast cancer.