Tumor susceptibility of p21(Waf1/Cip1)-deficient mice

The cell cycle regulator p21 mediates the ability of the tumor suppressor p 53 to arrest cellular proliferation. We have examined the involvement of p2 1 in tumor suppression by following a large cohort of p21-deficient mice fo r an extended period of time. We report that p21-deficient mice develop spo ntaneous tumors at an average age of 16 months, whereas wild-type mice are tumor-free beyond 2 years of age. The tumors arising in p21-null mice deriv e from a variety of cell types and include hematopoietic (similar to 65% of the tumors), endothelial (similar to 20%), and epithelial (similar to 10%) tumors. We have also studied radiation-induced carcinogenesis to test whet her, in this setting, p53 exerts its tumor suppressor activity mainly throu gh apoptosis, rather than through p21-mediated cell-cycle arrest. Concurrin g with this, p21-deficient mice did not show increased susceptibility to ra diation-induced carcinogenesis. On the contrary, they were protected relati ve to wild-type mice. We conclude that p21, by mediating p53-dependent cell -cycle arrests plays a significant role in tumor suppression.