Inducible Transgenic Models of BRCA1 Function
Abstract
Germ line mutations in the breast and ovarian cancer susceptibility gene, BRCA1, account for a large proportion of families with inherited breast and ovarian cancer. Interestingly, while germ line BRCA1 mutations predispose carriers to adenocarcinoma of the breast, no somatic BRCA1 mutations have been found in sporadic primary breast cancers. This observation suggests that this molecule may normally protect the breast against carcinogenesis only during specific stages of mammary gland development. Previously, we have analyzed the temporal and spatial pattern of BRCA1 expression during normal mouse embryogenesis, in adult tissues, and during postnatal mammary gland development. These studies support a role for BRCA1 in the regulation of cell proliferation and differentiation in the breast during puberty and pregnancy. We hypothesize that BRCA1 plays a critical role in mammary gland development, and that its function is temporally restricted to particular developmental phases. In this application, we propose to test this hypothesis by using a modified tetracycline-inducible expression system to either induce or abolish BRCA1 expression in transgenic mice during particular developmental stages in a temporally-restricted and breast-specific manner. Through this approach, we hope to understand more clearly how the loss or mutation of this molecule contributes to carcinogenesis in a developmental-specific manner.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1999
- Accession Number
- ADB259312
Entities
People
- Lewis A Chodosh
Organizations
- University of Pennsylvania