title: Tumor susceptibility of p21(Waf1/Cip1)-deficient mice.
abstract: The cell cycle regulator p21 mediates the ability of the tumor suppressor p53 to arrest cellular proliferation. We have examined the involvement of p21 in tumor suppression by following a large cohort of p21-deficient mice for an extended period of time. We report that p21-deficient mice develop spontaneous 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 derive from a variety of cell types and include hematopoietic ( approximately 65% of the tumors), endothelial ( approximately 20%), and epithelial ( approximately 10%) tumors. We have also studied radiation-induced carcinogenesis to test whether, in this setting, p53 exerts its tumor suppressor activity mainly through apoptosis, rather than through p21-mediated cell-cycle arrest. Concurring with this, p21-deficient mice did not show increased susceptibility to radiation-induced carcinogenesis. On the contrary, they were protected relative to wild-type mice. We conclude that p21, by mediating p53-dependent cell-cycle arrest, plays a significant role in tumor suppression.
authors.affiliation: Department of Immunology and Oncology, National Center of Biotechnology (Spanish Council for Scientific Research), Campus de Cantoblanco, Madrid E-28049, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Martín-Caballero
authors.forename: J M
authors.initials: JM
authors.lastname: Flores
authors.forename: P
authors.initials: P
authors.lastname: García-Palencia
authors.forename: M
authors.initials: M
authors.lastname: Serrano
mesh_terms: D000818:Animals; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009374:Neoplasms, Experimental / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D009381:Neoplasms, Radiation-Induced / Q000209:etiology / Q000235:genetics / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
chemical_list: C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016159:Tumor Suppressor Protein p53