title: p21Cip1 nullizygosity increases tumor metastasis in irradiated mice.
abstract: p21(Cip1) is a cyclin-dependent kinase inhibitor whose abundance increases in cells exposed to radiation or other DNA-damaging agents. Such increases activate a G1 checkpoint, which allows time for DNA repair before S phase entry. By inhibiting cell cycle progression, p21(Cip1) potentially suppresses tumorigenesis, and in support, we show that p21(Cip1) heterozygous and nullizygous mice develop more tumors than do wild-type mice when exposed to a single dose of gamma-irradiation. Importantly, we also show that p21(Cip1) nullizygosity increases the incidence of metastatic tumors in irradiated mice. We suggest that p21(Cip1) is haploinsufficient for tumor suppression and functions as an antimetastatic agent.
authors.affiliation: Molecular Oncology Program, H. Lee Moffitt Cancer Center and Research Institute, and Department of Interdisciplinary Oncology, University of South Florida College of Medicine, Tampa, Florida 33612, USA.
authors.forename: Rosalind J
authors.initials: RJ
authors.lastname: Jackson
authors.forename: Robert W
authors.initials: RW
authors.lastname: Engelman
authors.forename: Domenico
authors.initials: D
authors.lastname: Coppola
authors.forename: Alan B
authors.initials: AB
authors.lastname: Cantor
authors.forename: Walker
authors.initials: W
authors.lastname: Wharton
authors.forename: W Jack
authors.initials: WJ
authors.lastname: Pledger
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000528:radiation effects; D003433:Crosses, Genetic; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics / Q000502:physiology*; D004249:DNA Damage; D004260:DNA Repair; D005720:Gamma Rays / Q000009:adverse effects; D017353:Gene Deletion; D018816:Genes, cdc; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis / Q000235:genetics*; D009381:Neoplasms, Radiation-Induced / Q000235:genetics / Q000473:pathology*; D009928:Organ Specificity; D011836:Radiation Tolerance / Q000235:genetics*
chemical_list: C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins