Cyclin D1, Anchorage-Independent Growth and Breast Cancer
Abstract
Derangements in the cell cycle machinery contribute to uncontrolled cell growth and tumorigenesis. Regulators of G1 progression including cyclin D1 and the cyclin-dependent kinase inhibitors p21 and p27 appear to be of particular importance in the pathogenesis of breast cancer. We suggest that aggressive breast cancer will involve both (i) overexpression of cyclin D1 and (ii) the failure to undergo a compensatory upregulation of cdk inhibitors. The specific aims are designed to test these hypotheses in cell culture models, nude mice, and breast cancer biopsies. We have generated mouse embryo fibroblasts (MEFs) that stably express a tetracycline-regulated cyclin D1 construct. In contrast to the data in NIH-3T3 cells, there was no compensatory upregulation of p2l in MEFs despite significant overexpression of cyclin D1. This may be due to the acquisition of p53 mutations. In addition, human breast cancer tissues have been analyzed for cyclin D1, p27 and Ki67 expression. Following optimization of p21 staining and analysis, correlation with prognostic factors will be performed.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1999
- Accession Number
- ADA388035
Entities
People
- Catherine Welsh
Organizations
- University of Miami