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%IPl and p27kiPl, appear to be particularly important in the pathogenesis of breast cancer. We suggested that aggressive breast cancer would involve both (i)overexpression of cyclin Dl and (ii) failure to undergo a compensatory upregulation of cdk inhibitors. The specific aims were designed to test these hypotheses in cell culture models, nude mice, and breast cancer biopsies. We 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 also failed to show a relationship between levels of cyclin Dl and the cdk inhibitors, supporting the MEF data. Expression of cyclin Dl, p27, and p21 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, 2001
- Accession Number
- ADA405221
Entities
People
- Catherine Welsh
Organizations
- University of Miami