Correction: Oncogenic Transformation by Inhibitor-Sensitive and -Resistant EGFR Mutants

Abstract

[This corrects the article DOI: 10.1371/journal.pmed.0020313.].

Fig 4. Sensitivity of Cell Transformation Induced by Expression of Mutant EGFR Characterized by Missense Mutation or Exon 19 Deletion, but not Exon 20 Insertion, to Gefitinib and Erlotinib.

(A) Anchorage-independent growth of clonal NIH-3T3 cells transformed with mutant EGFR or EGF-stimulated wild-type EGFR treated with the indicated concentrations of erlotinib immediately prior to suspension in soft agar. Transformation induced by expression of L858R, G719S, and L747_E749del A750P EGFR, but not EGF-stimulated wild-type EGFR or D770_N771insNPG EGFR, was inhibited by 0.1 μM erlotinib. Representative photographs are shown. (B) Number of colonies formed in soft agar by clonal NIH-3T3 cells expressing L858R EGFR and D770_N771insNPG EGFR treated with the indicated concentrations of gefitinib or erlotinib immediately prior to suspension in soft agar. Transformation by cells expressing the L858R EGFR was inhibited by 0.1 μM gefitinib or erlotinib, whereas transformation by cells expressing the insertion mutant was resistant to low concentrations of these inhibitors. Colonies were quantitated by counting ten fields each of triplicate wells photographed with a 10x objective; mean ± standard deviation is shown. Ins, D770_N771insNPG EGFR. (C) Transformation induced by expression of D770_N771insNPG EGFR is inhibited 10-fold more efficiently by the irreversible EGFR inhibitor CL-387,785 [35]. Clonal NIH-3T3 cells expressing the insertion mutant were treated with the indicated concentrations of gefitinib, erlotinib, or CL-387,785 immediately prior to suspension in soft agar. This assay was not done in triplicate, but the results are representative of two independent experiments. The number of colonies was normalized to maximum colony formation for each treatment, and sigmoidal dose response curves were fitted to the data using Prism Graphpad software to determine IC50s.