Role of Changes in the Expression of Cyclins and Retinoblastoma Protein in the Development of Breast Cancer
Abstract
The expression levels of a total of 15 cell cycle regulatory proteins have been determined in a panel of breast cancer and normal breast epithelial cell lines, as well as in a number of breast tissue and normal breast epithelial tissue samples. The results of these analyses indicate the presence of a defect in the expression of cyclin D1, Rb and/or the cyclin dependent kinase inhibitor protein, p16, in essentially all the breast cancer cell lines and tissues studied. The degree of overexpression of cyclin D1 is most closely reflected by changes in mRNA levels, although gene amplification and in one case an increase in half-life of the protein also contribute. Homozygous deletion of the p16 gene has been found to be a frequent mechanism for the absence of this tumor suppressor protein in breast cancer. Construction of replication incompetent adenovirus vectors for high efficiency transfection of breast cancer cells with genes encoding antisense cyclin D1 and sense p16 has been essentially completed. Human breast cancer cell lines tumorigenic in nude mice have been identified and will be transfected with these adenoviral vectors to directly test and confirm the role of cyclin D1 and p16 expression in breast cell tumorigenicity.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1996
- Accession Number
- ADB222571
Entities
People
- Thomas A. Langan
Organizations
- University of Colorado Boulder