FIGURE 2.

Estrogen receptor inhibition with fulvestrant induces upregulation of PI3K signaling. Ovariectomized athymic mice were s.c. implanted with MCF-7 cells and a 10-day-release E2 pellet (0.12 mg). Twelve days later, mice were randomized to treatment with vehicle or fulvestrant (5 mg/week, s.c., clinical formulation). Tumors were harvested after 3–4 weeks of treatment. Tumor lysates were analyzed by immunoblotting using the indicated antibodies; each lane contains equal amount of protein from two to three tumors. Fulvestrant treatment decreased the levels of ER and ER-regulated genes products (PR, IGF-1R), but increased levels of P-AKT-T308 and P-AKT-S473, suggesting increased activation of PI3K. All lanes were from the same membrane.