Tissue Specific Activation and Inactivation of the Neu Proto-Oncogene in Transgenic Mice Using Cre Recombinase
Abstract
20 TO 30% OF HUMAN BREAST CANCERS AMPLIFY AND OVEREXPRESS ErbE2 (HER2, Neu). To examine the role of this receptor tyrosine kinase in both normally mammary gland development and in mammary tumorigenesis, I have created several mouse models. To examine the role of ErbB2 in mouse mammary development I have utilized Cre/loxP technology to create a mammary specific knockout of ErbB2. Although the loxP flanked construct was shown to be functional, as were the transgenic mice expressing Cre in the mammary epithelium, we have not yet observed mammary specific inactivation of ErbB2. This is likely due to background specific methylation of the transgene and we have completely introgressed the mice onto an FVB background. To examine the role of ErbB2 in mammary tumorigenesis, I have created a mouse model that expresses activated ErbB2 specifically in the mammary gland. This resulted in mammary adenocarcinomas that amplified and overexpressed ErbB2, closely mimicking the human condition. Further, the mammary epithelium escapes from the normal confines of the stroma in these mice. Additional experiments have revealed double minute chromosomes, overexpression of various genes and I have now isolated three cell lines from the tumors in order to examine these tumors more fully.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2001
- Accession Number
- ADB282777
Entities
People
- Eran R Andrechek
- William A Muller
Organizations
- McMaster University