Development of spontaneous mammary tumors in BALB/c p53 heterozygous mice: A model for Li-Fraumeni syndrome

Charlotte Kuperwasser, Gregory D. Hurlbut, Frances S. Kittrell, Ellen S. Dickinson, Rodolfo Laucirica, Daniel Medina, Stephen P. Naber, D. Joseph Jerry

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Abstract

Breast cancer is the most frequent tumor type among women in the United States and in individuals with Li-Fraumeni syndrome. The p53 tumor suppressor gene is altered in a large proportion of both spontaneous breast malignancies and Li-Fraumeni breast cancers. This suggests that loss of p53 can accelerate breast tumorigenesis, yet p53-deficient mice rarely develop mammary tumors. To evaluate the effect of p53 loss on mammary tumor formation, the p53(null) allele was back-crossed onto the BALB/c genetic background. Median survival was 15.4 weeks for BALB/c-p53(-/-) mice compared to 54 weeks for BALB/c-p53(+/-) mice. Sarcomas and lymphomas were the most frequent tumor types in BALB/c-p53(-/-) mice, whereas 55% of the female BALB/c-p53(+/-) mice developed mammary carcinomas. The mammary tumors were highly aneuploid, frequently lost the remaining wild-type p53 allele, but rarely lost BRCA1. Although mammary tumors were rarely detected in BALB/c-p53(-/-) female mice, when glands from BALB/c-p53(-/-) mice were transplanted into wild-type BALB/c hosts, 75% developed mammary tumors. The high rate of mammary tumor development in the BALB/c background, but not C57B1/6 or 129/Sv, suggests a genetic predisposition toward mammary tumorigenesis. Therefore, the BALB/c-p53(+/-) mice provide a unique model for the study of breast cancer in Li-Fraumeni syndrome. These results demonstrate the critical role that the p53 tumor suppressor gene plays in preventing tumorigenesis in the mammary gland.

Original languageEnglish (US)
Pages (from-to)2151-2159
Number of pages9
JournalAmerican Journal of Pathology
Volume157
Issue number6
DOIs
StatePublished - Jan 1 2000

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Li-Fraumeni Syndrome
Breast Neoplasms
Carcinogenesis
Breast
Tumor Suppressor Genes
Alleles
Neoplasms
Aneuploidy
Human Mammary Glands
Genetic Predisposition to Disease
Sarcoma
Lymphoma

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Kuperwasser, C., Hurlbut, G. D., Kittrell, F. S., Dickinson, E. S., Laucirica, R., Medina, D., ... Joseph Jerry, D. (2000). Development of spontaneous mammary tumors in BALB/c p53 heterozygous mice: A model for Li-Fraumeni syndrome. American Journal of Pathology, 157(6), 2151-2159. https://doi.org/10.1016/S0002-9440(10)64853-5

Development of spontaneous mammary tumors in BALB/c p53 heterozygous mice : A model for Li-Fraumeni syndrome. / Kuperwasser, Charlotte; Hurlbut, Gregory D.; Kittrell, Frances S.; Dickinson, Ellen S.; Laucirica, Rodolfo; Medina, Daniel; Naber, Stephen P.; Joseph Jerry, D.

In: American Journal of Pathology, Vol. 157, No. 6, 01.01.2000, p. 2151-2159.

Research output: Contribution to journalArticle

Kuperwasser, C, Hurlbut, GD, Kittrell, FS, Dickinson, ES, Laucirica, R, Medina, D, Naber, SP & Joseph Jerry, D 2000, 'Development of spontaneous mammary tumors in BALB/c p53 heterozygous mice: A model for Li-Fraumeni syndrome', American Journal of Pathology, vol. 157, no. 6, pp. 2151-2159. https://doi.org/10.1016/S0002-9440(10)64853-5
Kuperwasser, Charlotte ; Hurlbut, Gregory D. ; Kittrell, Frances S. ; Dickinson, Ellen S. ; Laucirica, Rodolfo ; Medina, Daniel ; Naber, Stephen P. ; Joseph Jerry, D. / Development of spontaneous mammary tumors in BALB/c p53 heterozygous mice : A model for Li-Fraumeni syndrome. In: American Journal of Pathology. 2000 ; Vol. 157, No. 6. pp. 2151-2159.
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