Figure 7. Pharmacologic attenuation of ERK activity suppresses oncogenic Ras–induced senescence.

(A) WT adult lung fibroblasts were infected with Hras^V12 retrovirus, treated with the MEK inhibitor U0126 at the indicated concentrations, and stained for SA–β-gal activity. Percent SA–β-gal–positive cells was also quantified. Data represent mean ± SEM. Scale bars: 200 μm. (B) WT lung fibroblasts infected with Hras^V12 retrovirus were treated with U0126 at the indicated concentrations for 3 days and probed for pERK, ERK, p19^ARF, p53, and p21^cip1 by immunoblotting. (C) A p53-dependent positive feedback role for TSP-1 in the maintenance of oncogenic Ras–induced senescence by tethering pERK in the cytoplasm.