Figure 8.

The anti-HER3 D1 Abs 16D3-C1 and 9F7-F11 and the anti-HER3 D3 Ab H4B-121 inhibit NRG-induced phosphorylation of HER3 as well as of AKT, leading to reduced phosphorylation of the downstream targets MDM2, XIAP, FoxO1, and GSK-3 (A) and to HER3 down-regulation (B). BxPC3 carcinoma cells were incubated with anti-HER3 Abs or the control Ab Px for various times and then stimulated with NRG for 10 minutes. Phosphorylation was analyzed after 15-minute Ab incubation at 37°C by Western blot analysis using the appropriate Abs. HER3 down-regulation was determined after Ab incubation at 37°C or 4°C for 15 minutes, 1 hour, and 2 hours. M, medium.