Modulation of nuclear receptor signaling by IGFBP-3. (A) RAR signaling. Luciferase activity was measured in LAPC-4 human prostate cancer cells cultured in the presence or absence of 10^–6 M ATRA and was transfected with IGFBP-3–expressing vector or control vector and with a vector expressing the RAR in which the DBD was replaced by the GAL4 DBD and with a GAL4 control vector. Each point represents the mean ± SD of 3 independent experiments performed in triplicate and normalized for GAL4 activity. (B) VDR signaling. Similar to panel A, except that cells were cultured in the presence or absence of 10^–6 M of the vitamin D analog EB1089 and cotransfected with a vector expressing the VDR in which the DBD was replaced by the GAL4 DBD. (C) RXR signaling. Similar to panel A, except cells were cultured in the presence or absence of 10^–6 M of the RXR-selective agonist AGN194204 and were cotransfected with a vector expressing the RXR in which the DBD was replaced by the GAL4 DBD.