Expression of a Truncated Brca1 Protein delays Lactational Mammary Development in Transgenic Mice
Document Type
Article
Department
Pathology and Microbiology
Abstract
To address the hypothesis that certain disease-associated mutants of the breast-ovarian cancer susceptibility gene BRCA1 have biological activity in vivo, we have expressed a truncated Brca1 protein (trBrca1) in cell-lines and in the mammary gland of transgenic mice. Immunofluorescent analysis of transfected cell-lines indicates that trBRCA1 is a stable protein and that it is localized in the cell cytoplasm. Functional analysis of these cell-lines indicates that expression of trBRCA1 confers an increased radiosensitivity phenotype on mammary epithelial cells, consistent with abrogation of the BRCA1 pathway. MMTV-trBrca1 transgenic mice from two independent lines displayed a delay in lactational mammary gland development, as demonstrated by altered histological profiles of lobuloalveolar structures. Cellular and molecular analyses indicate that this phenotype results from a defect in differentiation, rather than altered rates of proliferation or apoptosis. The results presented in this paper are consistent with trBrca1 possessing dominant-negative activity and playing an important role in regulating normal mammary development. They may also have implications for germline carriers of BRCA1 mutations.
Publication (Name of Journal)
Transgenic Research
Recommended Citation
Brown, M. A.,
Nicolai, H.,
Howe, K.,
Katagiri, T.,
Lalani, E.,
Simpson, K. J.,
Manning, N. W.,
Deans, A.,
Chen, P.,
Khanna, K. K.,
Wati, M. R.,
Griffiths, B. L.,
Xu, C. F.,
Stamp, G. W.,
Solomon, E.
(2002). Expression of a Truncated Brca1 Protein delays Lactational Mammary Development in Transgenic Mice. Transgenic Research, 11(5), 467-478.
Available at:
https://ecommons.aku.edu/pakistan_fhs_mc_pathol_microbiol/352