Journal: Molecular Oncology

Article Title: Recurrent cancer‐associated ERBB4 mutations are transforming and confer resistance to targeted therapies

doi: 10.1002/1878-0261.70189

Figure Lengend Snippet: Transforming ERBB4 mutants are sensitive to pan‐ERBB inhibitors. (A) Sensitivity of Ba/F3 cells expressing different ERBB4 variants to pan‐ERBB inhibitors. Ba/F3 cells expressing ERBB4 variants, growing in the absence of IL3 and presence of NRG‐1 (10% serum), and vector control cells growing in the presence of IL3 were treated with the indicated concentrations of pan‐ERBB inhibitors (neratinib, afatinib or dacomitinib) for 72 h and cell viability was measured with the MTT assay. A representative dose–response curve with mean and SD of quadruplicate analyses of one of independent experiments ( n = 3 (E452K, R711C n = 2)) is shown for each inhibitor. (B) Fold changes in IC50 for Ba/F3 cells expressing ERBB4 variants, compared to Ba/F3 cells expressing wild‐type ERBB4 are shown for each replicate experiment from A ( n = 3 (E452K, R711C n = 2)). * P < 0.05; one‐sample t test, P ‐values corrected for multiple comparisons by Bonferroni method. Horizontal lines indicate geometric means of the replicate experiments.

Article Snippet: The cells were incubated in the presence of 0.00067–2.5 μ m of neratinib (Puma Biotechnology), afatinib (Boehringer Ingelheim am Rhein, Germany), dacomitinib (Cayman Chemicals, Ann Arbor, MI, USA) or DMSO only for 72 h before measuring cell viability of quadruplicate samples with MTT assay (as described above).

Techniques: Expressing, Plasmid Preparation, Control, MTT Assay