Document Detail

Conditional mutation of Brca1 in mammary epithelial cells results in blunted ductal morphogenesis and tumour formation.
MedLine Citation:
PMID:  10319859     Owner:  NLM     Status:  MEDLINE    
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.
X Xu; K U Wagner; D Larson; Z Weaver; C Li; T Ried; L Hennighausen; A Wynshaw-Boris; C X Deng
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Nature genetics     Volume:  22     ISSN:  1061-4036     ISO Abbreviation:  Nat. Genet.     Publication Date:  1999 May 
Date Detail:
Created Date:  1999-05-25     Completed Date:  1999-05-25     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9216904     Medline TA:  Nat Genet     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  37-43     Citation Subset:  IM    
Genetics of Development and Disease Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
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MeSH Terms
Apoptosis / genetics
BRCA1 Protein / genetics*
Cell Line
Epithelial Cells / metabolism*,  pathology
Genes, p53 / genetics
Mammary Glands, Animal / growth & development*,  metabolism,  pathology
Mammary Neoplasms, Animal / genetics*,  pathology
Mice, Inbred Strains
Translocation, Genetic
Reg. No./Substance:
0/BRCA1 Protein
Comment In:
Nat Genet. 1999 May;22(1):10   [PMID:  10319850 ]

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