| Autor: |
Brown, Melissa, Nicolai, Hans, Howe, Kathy, Katagiri, Toyomasa, Lalani, El-Nasir, Simpson, Kaylene, Manning, Nathan, Deans, Andrew, Chen, Phil, Khanna, Kum, Wati, Mas, Griffiths, Beatrice, Xu, Chun-Fang, Stamp, Gordon, Solomon, Ellen |
| Zdroj: |
Transgenic Research; Oct2002, Vol. 11 Issue 5, p467-478, 12p |
| Abstrakt: |
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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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