title: p53-dependent apoptosis suppresses tumor growth and progression in vivo.
abstract: To determine the contribution of p53 loss to tumor progression, we have induced abnormal proliferation in the brain choroid plexus epithelium of transgenic mice using a SV40 T antigen fragment that perturbs pRB family function but does not affect p53 function. Tumors induced by this mutant develop slowly compared with those induced by wild-type T antigen. Suppressed tumor growth is directly attributable to p53 function, since rapid tumor development occurs when the T antigen fragment is expressed in p53-null mice. In p53-heterozygous mice, stochastic loss of the wild-type p53 allele results in the focal emergence of aggressive tumor nodules characteristic of tumor progression. In each case, aggressive tumor development in the absence of p53 function corresponds to a decrease in the level of apoptosis. These results provide in vivo evidence that p53-dependent apoptosis, occurring in response to oncogenic events, is a critical regulator of tumorigenesis.
authors.affiliation: Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill 27599.
authors.forename: H
authors.initials: H
authors.lastname: Symonds
authors.forename: L
authors.initials: L
authors.lastname: Krall
authors.forename: L
authors.initials: L
authors.lastname: Remington
authors.forename: M
authors.initials: M
authors.lastname: Saenz-Robles
authors.forename: S
authors.initials: S
authors.lastname: Lowe
authors.forename: T
authors.initials: T
authors.lastname: Jacks
authors.forename: T
authors.initials: T
authors.lastname: Van Dyke
mesh_terms: D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic; D002831:Choroid Plexus / Q000502:physiology; D016545:Choroid Plexus Neoplasms / Q000235:genetics / Q000473:pathology*; D003433:Crosses, Genetic; D004848:Epithelium; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
chemical_list: D000952:Antigens, Polyomavirus Transforming; D016159:Tumor Suppressor Protein p53