Fig. 1

A Lapatinib response varies across 20 HER2⁺ breast cancer cell lines as measured by GI50 metrics. Cell lines to the right are more resistant, with the –log(GI50) set to the maximum dose tested. Error bars represent ± Standard Deviation (S.D.). B Heatmap of relative expression of genes that are differentially expressed by 20-fold or more between resistant and sensitive cell lines. The top 20 genes more highly expressed in resistant cells were selected for siRNA knockdown. C Cell growth relative to untreated control cells for JIMT1 and 21-MT1 cells treated with siRNAs against the top 20 genes from (C). Significant hits were deemed to be those that had cell viability at or below a value 1.5 S.D. from the mean, as described previously [19]. Error bars are ± S.D. D Analysis of protein (left panel) by Western blot and gene (right panel) expression by q-RT-PCR show that INHBA protein and transcript levels are decreased following siRNA knockdown. The knockdown of INHBA by siRNA Q4 results in 4.9% expression relative to control, while Q6 results in 11.8% expression