Figure 8. Imatinib treatment blocks ΔNp63α/TAp73 dissociation, TAp73-dependent transcription, and cell death induced by cisplatin.

(A) Imatinib attenuated dissociation of ΔNp63α and TAp73. In left blots (control), cells were treated with imatinib (1 μM for 8 hours) or vehicle control; in right blots, cells were pretreated with imatinib (1 μM for 2 hours) or vehicle control, then treated with cisplatin (IC₇₀ for 6 hours) prior to IP for p63 or p73. Dissociation of TAp73 and ΔNp63α following cisplatin treatment (compare lanes 3 and 11) was attenuated by imatinib treatment (lane 15). (B and C) TAp73-dependent proapoptotic transcription required c-Abl–mediated phosphorylation. HCC-1937 cells (B) or MDA-MB-468 cells (C) were pretreated with imatinib (1 μM for 2 hours) and/or treated with cisplatin (IC₈₀ for 6 hours) as indicated, and mRNA was analyzed by QRT-PCR. (D) c-Abl–dependent phosphorylation is important for cisplatin sensitivity. Cells were pretreated with imatinib as in C, then treated with cisplatin (IC₇₀) and analyzed for viability by MTT at 3 days. Error bars show SD for 3 independent experiments.