NR3C1 and breast cancer: Using knock-in (KI) mice harboring wild-type PTEN, a PTEN lipid phosphatase-deficient mutant (PTEN G129E), or a PTEN phosphatase dead mutant (PTEN C124S), Yip et al. found that, although the loss of the PTEN-lipid-phosphatase function cooperates with oncogenic PI3K to promote rapid mammary tumorigenesis, the additional loss of PTEN-protein-phosphatase activity triggered an extensive cell-death response that was evident in early and advanced mammary tumors, which points out that the dual regulation of GR by PI3K and PTEN functions as a rheostat.