Cyclin E, A Potential Prognostic Marker in Breast Cancer
Abstract
We have established the use of cyclin E as a prognostic marker for breast cancer. Tumor specimens from 400 breast cancer patients were examined; changes of cyclin E expression were compared with seven other established tumor markers to patient outcome. Altered expression of cyclin E was observed in 90% of all breast cancers with poor prognosis where patients either died of breast cancer or were still with cancer at the last contact date. Similarly in 85% of all breast cancer patients where cyclin E was either not altered, or its alteration was minimal, patients had a favorable prognosis. We have also characterized the nature of overexpression and alteration of cyclin E in breast cancer cells in vitro and have found and reported that cyclin E forms an active complex with cdk2 constitutively throughout the tumor cell cycle while this complex is only active in the G1-S transition in normal cells. We have also found that cyclin E, if overexpressed in tumor cells, can bypass the cyclin D-pRb feedback loop and act redundantly and provides tumor cells with yet another mechanism to gain a growth advantage. Lastly, studies using the drug Lovastatin demonstrated that this highly prescribed drug used to lower cholesterol levels is also capable of inducing all four cyclin dependent kinase inhibitors (CKIs) in a cell specific manner via cell cycle independent mechanism. Since the CKIs directly inhibit the activity of cyclin E/cdk2 complexes, future work to elucidate the mechanism of induction in tumor cells could have significant therapeutic implications.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1998
- Accession Number
- ADA368551
Entities
People
- Khandan Keyomarsi