Brca2 Deficiency Does Not Impair Mammary Epithelium Development but Promotes Mammary Adenocarcinoma Formation in p53+/- Mutant Mice

Alison M.Y. Cheung, Andrew Elia, Ming Sound Tsao, Susan Done, Kay Uwe Wagner, Lothar Hennighausen, Razqallah Hakem, Tak W. Mak

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Brca2 is an important tumor suppressor associated with susceptibility to breast cancer. Although increasing evidence indicates that the primary function of Brca2 is to facilitate the repair of DNA damage via the homologous recombination pathway, how Brca2 prevents breast cancer is largely unknown. To study the role of Brca2 specifically in mammary epithelium development, we crossed mice bearing the conditionally deficient allele Brca2 flox9-10 to mouse mammary tumor virus- or whey acidic protein-Cre transgenic lines. Analysis of these animals showed that Brca2 is not required for epithelial expansion in mammary glands of pregnant mice. In addition, examination of mammary gland involution revealed normal kinetics of mammary alveolar cell apoptosis after weaning of litters. Nevertheless, Brca2-deficient mice developed mammary adenocarcinomas after a long latency (average, 1.6 years). Detailed histopathological analysis of four of these tumors demonstrated that three of them showed abnormal p53 protein expression. A mutation in the p53 gene was detected in one case. Moreover, homozygosity versus heterozygosity for the Brca2 mutation heavily skewed the tumor spectrum toward mammary adenocarcinoma development in p53+/- mice. Our data indicate that Brca2 is not essential for mammary epithelium development but that Brca2 deficiency and down-regulated p53 expression can work jointly to promote mammary tumorigenesis.

Original languageEnglish (US)
Pages (from-to)1959-1965
Number of pages7
JournalCancer Research
Volume64
Issue number6
DOIs
StatePublished - Mar 15 2004

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Cheung, A. M. Y., Elia, A., Tsao, M. S., Done, S., Wagner, K. U., Hennighausen, L., Hakem, R., & Mak, T. W. (2004). Brca2 Deficiency Does Not Impair Mammary Epithelium Development but Promotes Mammary Adenocarcinoma Formation in p53+/- Mutant Mice. Cancer Research, 64(6), 1959-1965. https://doi.org/10.1158/0008-5472.CAN-03-2270