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. Author manuscript; available in PMC: 2010 Jul 28.
Published in final edited form as: Oncogene. 2009 Nov 2;29(4):589–596. doi: 10.1038/onc.2009.366

Figure 4.

Figure 4

Notch3 and EGFR/ras/MAPK pathways cooperate in regulating Bim expression. (A) Bim is upregulated when HCC2429 was transfected with Notch3 siRNA as compared to control at 0 times, whereas inhibition of Notch3 signaling does not increase Bim expression over treatment with U0126 alone at both 6 and 24 hours, suggesting that Notch3 regulates Bim expression mainly through pERK. (B) AG1478 alone slightly diminishes Bim expression. However, treatment with both AG1478 and N3SiRNA resultes in the synergistic induction of Bim, compared to either treatment alone. Inhibition of pERK and EGFR with U0126 (C) and AG1478 (D), respectively, preventing Notch3-dependent suppression of Bim, supporting the hypothesis that modulation of Bim and apoptosis in lung cancer by Notch3 is dependent on intact EGFR/ras/MAPK signaling.