title: Combined loss of p21(waf1/cip1) and p27(kip1) enhances tumorigenesis in mice.
abstract: The cell cycle inhibitors p21(Waf1/Cip1) and p27(Kip1) are frequently downregulated in many human cancers, and correlate with a worse prognosis. We show here that combined deficiency in p21 and p27 proteins in mice is linked to more aggressive spontaneous tumorigenesis, resulting in a decreased lifespan. The most common tumors developed in p21p27 double-null mice were endocrine, with a higher incidence of pituitary adenomas, pheochromocytomas and thyroid adenomas. The combined absence of p21 and p27 proteins delays the incidence of radiation-induced thymic lymphomas with a higher apoptotic rate, measured by active caspase-3 and cleaved PARP-1 immunoexpresion. These results provide experimental evidence for a cooperation of both cyclin-dependent kinase inhibitors in tumorigenesis in mice.
authors.affiliation: Department of Animal Medicine and Surgery, Veterinary School, Complutense University, Madrid, Spain.
authors.forename: Rosa A
authors.initials: RA
authors.lastname: García-Fernández
authors.forename: Pilar
authors.initials: P
authors.lastname: García-Palencia
authors.forename: María Á
authors.initials: MÁ
authors.lastname: Sánchez
authors.forename: Gabriel
authors.initials: G
authors.lastname: Gil-Gómez
authors.forename: Belén
authors.initials: B
authors.lastname: Sánchez
authors.forename: Eduardo
authors.initials: E
authors.lastname: Rollán
authors.forename: Juan
authors.initials: J
authors.lastname: Martín-Caballero
authors.forename: Juana M
authors.initials: JM
authors.lastname: Flores
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000172:deficiency* / Q000235:genetics; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000172:deficiency* / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D004701:Endocrine Gland Neoplasms / Q000235:genetics; D005838:Genotype; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D051379:Mice; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D016133:Polymerase Chain Reaction
chemical_list: C493957:Cdkn1a protein, mouse; C493961:Cdkn1b protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D017931:DNA Primers; D050760:Cyclin-Dependent Kinase Inhibitor p27; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3