Author:
Donehower L A,Godley L A,Aldaz C M,Pyle R,Shi Y P,Pinkel D,Gray J,Bradley A,Medina D,Varmus H E
Abstract
By crossing mice that carry a null allele of p53 with transgenic mice that develop mammary adenocarcinomas under the influence of a Wnt-1 transgene, we have studied the consequences of p53 deficiency in mammary gland neoplasia. In Wnt-1 transgenic mice homozygous for the p53 null allele, tumors appear at an earlier age than in animals heterozygous or wild-type at the p53 locus. About half of the tumors arising in p53 heterozygotes exhibit loss of the normal p53 allele, implying selection for p53-deficient cells. Mammary tumors lacking p53 display less fibrotic histopathology and increased genomic instability with aneuploidy, amplifications, and deletions, as detected by karyotype analysis and comparative genomic hybridization. In one tumor, the amplified region of chromosome 7 had an ectopically expressed int-2/FGF3 proto-oncogene, a gene known to cooperate with Wnt-1 in the production of mammary tumors. These findings favor a model in which p53 deficiency relaxes normal restraints on chromosomal number and organization during tumorigenesis.
Publisher
Cold Spring Harbor Laboratory
Subject
Developmental Biology,Genetics
Reference59 articles.
1. Nonrandom abnormalities involving chromosome 1 and Harvey-ras-1 alleles in rat mammary tumor progression.;Cancer Res.,1992
2. Molecular cloning and chromosomal mapping of DNA rearranged with parathyroid hormone gene in a parathyroid adenoma.;J. Clin. Invest,1989
3. Multiple independent activations of the neu oncogene by a point mutation altering the transmembrane domain of p185
4. Spontaneous immortalization of normal fibroblasts from patients with Li-Fraumeni cancer syndrome: Aneuploidy and immortalization.;Cancer Res.,1990
5. p53 Mutations, Another Breast Cancer Prognostic Factor
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