Conditional mutation of Brca1 in mammary epithelial cells results in blunted ductal morphogenesis and tumour formation
- 1 May 1999
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Genetics
- Vol. 22 (1), 37-43
- https://doi.org/10.1038/8743
Abstract
Cre-mediated excision of exon 11 of the breast-tumour suppressor gene Brca1 in mouse mammary epithelial cells causes increased apoptosis and abnormal ductal development. Mammary tumour formation occurs after long latency and is associated with genetic instability characterized by aneuploidy, chromosomal rearrangements or alteration of Trp53 (encoding p53) transcription. To directly test the role of p53 in Brca1-associated tumorigenesis, we introduced a Trp53-null allele into mice with mammary epithelium-specific inactivation of Brca1. The loss of p53 accelerated the formation of mammary tumours in these females. Our results demonstrate that disruption of Brca1 causes genetic instability and triggers further alterations, including the inactivation of p53, that lead to tumour formation.Keywords
This publication has 41 references indexed in Scilit:
- Epidemiology, prevention, and early detection of breast cancerCurrent Opinion in Oncology, 1997
- Hereditary breast cancerBritish Journal of Surgery, 1997
- Differential subcellular localization, expression and biological toxicity of BRCA1 and the splice variant BRCA1-Δ11bOncogene, 1997
- Localization of BRCA1 and a Splice Variant Identifies the Nuclear Localization SignalMolecular and Cellular Biology, 1997
- The BRCA1 and BRCA2 breast cancer genesCurrent Opinion in Oncology, 1997
- Isolation of the Mouse Homologue of BRCA1 and Genetic Mapping to Mouse Chromosome 11Genomics, 1995
- A Strong Candidate for the Breast and Ovarian Cancer Susceptibility Gene BRCA1Science, 1994
- Cloning the RAD51 homologue ofSchizosaccharomyces pombeNucleic Acids Research, 1993
- Cloning of human, mouse and fission yeast recombination genes homologous to RAD51 and recANature Genetics, 1993
- Rad51 protein involved in repair and recombination in S. cerevisiae is a RecA-like proteinCell, 1992