Supplementary Figure S6 from Relief of Feedback Inhibition of HER3 Transcription by RAF and MEK Inhibitors Attenuates Their Antitumor Effects in BRAF-Mutant Thyroid Carcinomas

Supplementary Figure S6 PDF file - 107K, Genetic knock-down or pharmacological inhibition of HER3 synergizes with PLX4032 and AZD6244, respectively, to inhibit growth of BRAF mutant thyroid cancer cells. A, SW1736 cells were treated with PLX4032 (0-2000 nM) with or without 1 �gM lapatinib or after stable expression of a shRNA to HER3. Indicated concentrations of PLX4032 and lapatinib were added at day 0 and day 3 and growth was measured 6 days after the first treatment. Points represent percent change (mean +/- SD) in cell count of triplicate wells compared to untreated cells. B, SW1736 cells were treated with 2 �gM PLX4032 or 100 nM AZD6244 and lysates collected at 1 and 72 h. Immunoblotting shows induction of pHER3 by both inhibitors. C, SW1736 and 8505C cells were treated with increasing concentrations of AZD6244 alone (open bars) or in combination with 1 �gM lapatinib (black). Cells were collected and counted after 4 days of treatment. Bars represent percent change (mean +/- SD) in cell counts of triplicate wells compared to untreated cells