Cyclin D1, Anchorage-Independent Growth and Breast Cancer
Abstract
Proteins that regulate progression through the G1 phase, including cyclin Dl and the cyclin-dependent kinase (cdk) inhibitors p2l to the cip1 and p27 to the kipl, appear to be particularly important in the pathogenesis of breast cancer. We suggest that aggressive breast cancer will involve both (1)overexpression of cyclin Dl and (2) 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 and inducibly overexpress cyclin Dl. In contrast to the data in NIH-3T3 cells, there was no compensatory upregulation of p2l in MEFs in response to cyclin Dl overexpression. An analysis of several established breast cancer cell lines has thus far failed to show a relationship between levels of cyclin Dl and the cdk inhibitors, supporting the MEK data. Expression of cyclin Dl, p27, and p2l have been analyzed in samples of human lobular carcinoma by immunohistochemistry. It appears that, unlike ductal carcinoma, cyclin Dl is preferentially overexpressed in invasive components of lobular carcinoma. In addition, whereas there was no correlation between cyclin Dl or p2l and proliferation markers, p27 levels demonstrated an inverse correlation with markers of proliferation in human lobular carcinoma.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2000
- Accession Number
- ADA388640
Entities
People
- Catherine Welsh
Organizations
- University of Miami