Deficiency of p53 accelerates mammary tumorigenesis in Wnt-1 transgenic mice and promotes chromosomal instability

L. A. Donehower, L. A. Godley, C. M. Aldaz, R. Pyle, Y. P. Shi, D. Pinkel, Joe Gray, A. Bradley, D. Medina, H. E. Varmus

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)882-895
Number of pages14
JournalGenes and Development
Volume9
Issue number7
StatePublished - 1995
Externally publishedYes

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Chromosomal Instability
Transgenic Mice
Carcinogenesis
Breast
Alleles
Neoplasms
Breast Neoplasms
Chromosomes, Human, Pair 7
Comparative Genomic Hybridization
Proto-Oncogenes
Genomic Instability
Aneuploidy
Human Mammary Glands
Heterozygote
Transgenes
Karyotype
Adenocarcinoma
Genes

Keywords

  • genomic instability
  • mammary tumors
  • mouse
  • p53
  • tumor model
  • Wnt-1

ASJC Scopus subject areas

  • Developmental Biology
  • Genetics

Cite this

Donehower, L. A., Godley, L. A., Aldaz, C. M., Pyle, R., Shi, Y. P., Pinkel, D., ... Varmus, H. E. (1995). Deficiency of p53 accelerates mammary tumorigenesis in Wnt-1 transgenic mice and promotes chromosomal instability. Genes and Development, 9(7), 882-895.

Deficiency of p53 accelerates mammary tumorigenesis in Wnt-1 transgenic mice and promotes chromosomal instability. / Donehower, L. A.; Godley, L. A.; Aldaz, C. M.; Pyle, R.; Shi, Y. P.; Pinkel, D.; Gray, Joe; Bradley, A.; Medina, D.; Varmus, H. E.

In: Genes and Development, Vol. 9, No. 7, 1995, p. 882-895.

Research output: Contribution to journalArticle

Donehower, LA, Godley, LA, Aldaz, CM, Pyle, R, Shi, YP, Pinkel, D, Gray, J, Bradley, A, Medina, D & Varmus, HE 1995, 'Deficiency of p53 accelerates mammary tumorigenesis in Wnt-1 transgenic mice and promotes chromosomal instability', Genes and Development, vol. 9, no. 7, pp. 882-895.
Donehower, L. A. ; Godley, L. A. ; Aldaz, C. M. ; Pyle, R. ; Shi, Y. P. ; Pinkel, D. ; Gray, Joe ; Bradley, A. ; Medina, D. ; Varmus, H. E. / Deficiency of p53 accelerates mammary tumorigenesis in Wnt-1 transgenic mice and promotes chromosomal instability. In: Genes and Development. 1995 ; Vol. 9, No. 7. pp. 882-895.
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