The Role of b-Catenin in Mammary Gland Carcinogenesis
Abstract
Wnt signaling molecules have been implicated in mouse mammary carcinogenesis. Beta-catenin, a downstream molecule in the Wnt pathway, activates transcription of target genes. Our studies are aimed at determining whether Beta-catenin can function as an oncogene in the mammary gland. Using the mouse as a model system, we targeted expression of Beta-catenin to the mammary gland in transgenic animals. Our results show that transgenic females develop mammary gland hyperplasia, with the majority of them proceeding to develop mammary gland tumors. The Beta-catenin tumors are characterized as microacinar adenocarcinomas, nearly identical to those found in Wnt-induced mouse models. We were also interested in identifying downstream transcriptional targets of Beta-catenin in the mammary gland. We have found cyclin D1 and c-myc, targets previously identified in other systems, to be upregulated in Beta-catenin mammary tumors and tumor cell lines. In an attempt to identify novel targets of Beta-catenin, mammary cell lines expressing inducible or constitutively activated Beta-catenin were generated, and a whole genome screen approach was taken. Several novel candidate target genes have been identified. Thus, our studies establish Beta-catenin as an oncogene in the mammary gland and have aided in the identification of gene targets in Beta-catenin-mediated mammary oncogenesis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2002
- Accession Number
- ADA405415
Entities
People
- Jennifer S. Michaelson
Organizations
- Harvard University