FIG. 7.

Linear activation of IGF-IR and EGFR is involved in E2-induced cell growth and cell death protection. A and B, Knockdown or blockade of IGF-IR and EGFR on ligand-induced cell growth. Cells were transiently transfected with nonspecific scrambled siRNA or siRNA against IGF-IR and EGFR (A) or pretreated with either 1 µm AG1024 or 1 µm AG1478 for 30 min (B). Then the cells were challenged with vehicle, E2 at 0.1 nm, 20 ng/ml IGF-I, or 20 ng/ml EGF for 4 d. Cell numbers were counted at the end of experiments. C, Effect of selective inhibitors on E2-induced cell death protection. MCF-7 cells were pretreated with either 1 µm AG1024 or 1 µm AG1478 for 30 min and then treated with vehicle, 0.1 nm E2, 20 ng/ml IGF-I, or 20 ng/ml EGF. Cell apoptosis was assayed on d 4 as described in Materials and Methods. Data are mean ± sem (n = 6). *, P < 0.05 comparing the siRNA-transfected or inhibitortreated cells with the growth factor-treated alone.