Changes in signal transduction pathway induced by gefitinib.

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Changes in signal transduction pathway induced by gefitinib. Changes in signal transduction pathway induced by gefitinib. A, protein lysates were prepared from breast cancer cells after treatment with 5 μmol/L gefitinib at the time points indicated, and protein expression levels were analyzed by Western blotting using specific antibodies. The Western blot results shown represent the results from a number of attempts, which showed similar trends. Inhibition of phospho-Akt (P-Akt) correlates with inhibition of phospho-FOXO3a (P-FOXO3a) and induction of FOXO3a targets, Bim and p27Kip1 in cells that are sensitive to gefitinib but not in nonsensitive cells. It should be noted that these experiments are designed to follow changes in protein expression during treatment, and because different exposures were used for different cell lines, no comparison between cell lines can be made from these blots. B, quantitative analysis of P-FOXO3a, P-Akt, and P-ERK 1/2 protein expression. Columns, mean results of two independent experiments after normalizing the data to t = 0 h; bars, SD. Statistical analysis has been done using Student's t test. *, P < 0.005; **, P < 0.001; ***, P < 0.05. Janna Krol et al. Mol Cancer Ther 2007;6:3169-3179 ©2007 by American Association for Cancer Research