The BRCA1 Tumor-Suppressor Gene in a Mouse Model of Breast Cancer.
Abstract
Mutations in the BRCAl locus account for approximately 45% of hereditary breast cancers in the United States (5). While expectations that mutant forms of this gene would also be observed in sporadic breast cancers have not been met, studies have found that the BRCAl RNA is underexpressed, or the protein mislocalized, in sporadic disease (1, 18). These studies indicate that BRCAl is a potential target in both hereditary and non hereditary breast cancer syndromes. Since the identification of the BRCAl gene in 1994 (13), a great deal of research has been focused on elucidating its function. BRCAl has been shown to be a nuclear phosphoprotein (2, 15, 17, 20) and that it interacts with a number of gene products, including E2A, BARD1, and RAD5l (9, 16, 19). By noting colocalization with RADS 1, and stabilization of this interaction following ionizing radiation, Scully et al suggested that BRCAl could function in double strand DNA break repair (16). Further evidence that BRCA 1 mutant cells have a defects in DNA repair have come from mice that lack BRCAl (BRKO). These mice die early in embryogenesis and blastocysts are sensitive to ionizing radiation (6, 8, 11, 12). Furthermore, embryonic lethality is partially alleviated by loss of p53 or p21, indicating that the absence of BRCA1 leads to a requirement for these gene products.(7).
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1997
- Accession Number
- ADA343826
Entities
People
- Timothy F. Lane
Organizations
- Harvard Medical School