The Role of a B-Catenin in Mammary Gland Development and Breast Cancer
Abstract
Many of the molecular events that control normal development of the mammary gland are the same events that, when misregulated, result in cancer. Therefore, the understanding of normal developmental processes in the mammary gland is a crucial first step to rational design of therapeutics which target these systems in breast cancer. The Wnt family of genes, which were first identified for their role in mouse mammary tumorigenesis, initiate a signaling cascade that manifests in the stabilization of beta-catenin protein. The proposed experiments are based on the hypothesis that misregulation of this pathway results in an accumulation of stabilized (beta-catenin, and genes involved in growth, cell death, and cell invasion are upregulated inappropriately, resulting in tumorigenesis. The proposed experiments use two methods to study beta-catenin's direct role in mammary gland development and tumorigenesis. Reconstitution experiments using retrovirally-transduced, stabilized (beta-catenin and transgenic mice expressing a dominant negative mutant beta-catenin (beta-catDN) specifically in the mammary gland provide opposite approaches for study. These two systems will be analyzed for changes in morphology, downstream gene expression, and flinctional differentiation, comparing gain- and loss-of-function of beta-catenin. Many factors implicated in mammary oncogenesis regulate beta-catenin, and beta-catenin is clearly involved in tumorigenesis in other organ systems, suggesting a role for beta-catenin in mammary oncogenesis. The proposed experiments will characterize beta-catenin's direct role in mammarv gland development and tumorigenesis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2001
- Accession Number
- ADA391314
Entities
People
- Jeffrey M. Rosen
- Stacey B. Tepera
Organizations
- Baylor College of Medicine