A mammary-specific model demonstrates the role of the p53 tumor suppressor gene in tumor development

D. J. Jerry, F. S. Kittrell, C. Kuperwasser, Rodolfo Laucirica, E. S. Dickinson, P. J. Bonilla, J. S. Butel, D. Medina

Research output: Contribution to journalArticle

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Abstract

Although alterations in the p53 tumor suppressor gene are detected frequently in human breast cancers, mammary tumors are observed infrequently in p53(null) mice. This has led to the suggestion that absence of p53 alone is not sufficient for induction of mammary tumors. However, early death of p53(null) mice from thymic lymphomas may obscure tumor phenotypes that would develop later. Therefore, p53(null) mammary epithelium was transplanted into cleared mammary fat pads of wild type p53 BALB/c hosts to allow long-term analysis of mammary tumor phenotypes. Five treatments were compared for their effects on tumor incidence in hosts bearing transplants of p53(null) and p53(wt) mammary epithelium. The treatment groups were: (1) untreated; (2) continuous hormone stimulation with pituitary isografts; (3) multiple pregnancies; (4) DMBA alone; and (5) DMBA + pituitary isografts. The tumor incidences in p53(null) vs p53(wt) mammary transplants for each treatment group were 62% vs 0%, 100% vs 0%, 68% vs 0%, 60% vs 4% and 91% vs 14%, respectively. The mammary tumors that developed in the p53(null) mammary epithelium were all adenocarcinomas and were frequently aneuploid. These data demonstrate that the absence of p53 is sufficient to cause development of mammary tumors and that hormonal stimulation enhances the tumorigenicity of p53(null) mammary epithelium to a greater extent than DMBA exposure alone. This model provides an in situ approach to examine the molecular basis for the role of p53 in the regulation of mammary tumorigenesis.

Original languageEnglish (US)
Pages (from-to)1052-1058
Number of pages7
JournalOncogene
Volume19
Issue number8
DOIs
StatePublished - Feb 21 2000

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Tumor Suppressor Genes
Breast
Breast Neoplasms
9,10-Dimethyl-1,2-benzanthracene
Epithelium
Neoplasms
Isografts
Transplants
Phenotype
Multiple Pregnancy
Incidence
Aneuploidy
Adipose Tissue
Lymphoma
Carcinogenesis
Adenocarcinoma
Hormones

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Jerry, D. J., Kittrell, F. S., Kuperwasser, C., Laucirica, R., Dickinson, E. S., Bonilla, P. J., ... Medina, D. (2000). A mammary-specific model demonstrates the role of the p53 tumor suppressor gene in tumor development. Oncogene, 19(8), 1052-1058. https://doi.org/10.1038/sj.onc.1203270

A mammary-specific model demonstrates the role of the p53 tumor suppressor gene in tumor development. / Jerry, D. J.; Kittrell, F. S.; Kuperwasser, C.; Laucirica, Rodolfo; Dickinson, E. S.; Bonilla, P. J.; Butel, J. S.; Medina, D.

In: Oncogene, Vol. 19, No. 8, 21.02.2000, p. 1052-1058.

Research output: Contribution to journalArticle

Jerry, DJ, Kittrell, FS, Kuperwasser, C, Laucirica, R, Dickinson, ES, Bonilla, PJ, Butel, JS & Medina, D 2000, 'A mammary-specific model demonstrates the role of the p53 tumor suppressor gene in tumor development', Oncogene, vol. 19, no. 8, pp. 1052-1058. https://doi.org/10.1038/sj.onc.1203270
Jerry, D. J. ; Kittrell, F. S. ; Kuperwasser, C. ; Laucirica, Rodolfo ; Dickinson, E. S. ; Bonilla, P. J. ; Butel, J. S. ; Medina, D. / A mammary-specific model demonstrates the role of the p53 tumor suppressor gene in tumor development. In: Oncogene. 2000 ; Vol. 19, No. 8. pp. 1052-1058.
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