The Role of Cyclin D1 Overexpression in Breast Cancer Progression.
Annual rept. 15 Jul 95-14 Jul 96,
COLUMBIA UNIV NEW YORK
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This project examines the role of cyclin Dl, and related genes, in multistage breast carcinogenesis. It may provide new biomarkers and strategies for the prevention and treatment of breast cancer. During the past year two studies were completed and published. The first provides further evidence that increased expression of cyclin D1 can inhibit the growth of mammary epithelial cells. It can also increase the sensitivity of these cells to the induction of apoptosis by various agents. These effects appear to be due to increased levels of the cell cycle inhibitory protein p27kip1. The second study demonstrates that increased expression of cyclin E in mammary epithelial cells can also inhibit growth and that this is also due to increased expression of p27kip1. Breast cancer cell lines with increased expression of cyclins D1 andor E also have high levels of p27kip1. Thus, mammary epithelial cells have a homeostatic feed-back loop that regulates the G1 to S progression of the cell cycle. Studies are in progress to evaluate the clinical relevance of these findings.
- Genetic Engineering and Molecular Biology
- Anatomy and Physiology
- Medicine and Medical Research