Fig. 8

Proposed model for MAPK inhibition in paired TP53^WT and TP53^MUT cell lines selected for resistance to MDM2 inhibitors. WM35-R (a) and SN40R2 (b) were selected from WM35 and SJSA-1 respectively and both were sensitive to growth inhibition by MAPK pathway inhibition. The TP53^MUT cells lost p53-dependent apoptosis but retained p53-independent cell cycle arrest and growth inhibition in response to inhibition of the MAPK pathway. SJSA-1 showed minimal p53-dependent apoptosis in response to MAPK pathway inhibition, plausibly resulting from p53 suppression by overexpression of MDM2