Figure 3.
Myc deletion causes an accumulation of MDM2. (a) MDM2 IHC showing no expression in intestinal crypts of wild type (AhCre Myc+/+) and a large increase of MDM2 expression in MYC-deficient (AhCre Mycfl/fl) mice in both nonirradiated and 14 Gy irradiated mice. Scale bars=25 μm. (b) Immunoblotting for MDM2 shows a marked increase in MDM2 protein levels in both nonirradiated and 14 Gy irradiated mice MYC-deficient intestines. (c) MYC-deficient mice treated with Nutlin exhibited a full restoration of the apoptotic response (* wt versus Myc, P =0.04, Mann Whitney n=3), which was not observed in MYC-deficient mice treated with vehicle. Note this restoration of apoptosis correlates with an induction of P53 in MYC-deficient mice treated with Nutlin. (d) Immunohistochemistry for P53 demonstrating that P53 now accumulates in nutlin-treated MYC-deficient intestines following gamma irradiation but not vehicle-treated or nonirradiated MYC-deficient intestines. Scale bars=50 μm