In addition, although tumor initiation occurred earlier in RIP-Tag2; p53−/−; Arf−/− compared to RIP-Tag2; p53−/−; Arf+/+ mice, by 12 weeks of age, no difference in tumor number was detected between mice of these genotypes (Figure 7B), suggesting that both p53-dependent and independent functions of Arf cooperate to suppress the angiogenic switch and tumor progression in this multi-stage carcinogenesis model. This evidence concerns the gene CDKN2A and neoplasm.