Interactions Between Cell Cycle Control Proteins and the Androgen Receptor in Prostate Cancer
Abstract
This project is based on our discovery that cyclin dependent kinase 6 (CDK6) can markedly stimulate the transcriptional activity of the androgen receptor (AR) in human prostate cancer cells. The research performed during the past year has confirmed and extended these findings and provided insights into the underlying mechanisms. Thus, we found that CDK6 can physically associate with the AR in vivo. Using a series of truncated and mutant forms of CDK6 that we constructed we obtained evidence that the cyclin Dl binding domain and the ATP binding site in CDK6 are not essential for the stimulatory effect of CDK6 on the AR. These results, taken together with additional findings, indicate that CDK6 can bind to and directly stimulate the activity of the AR via a cyclin Dl and kinase independent mechanism. Therefore, in addition to its role in cell cycle control, CDK6 may play an independent role in modulating the activity of the AR. Our findings may have clinical significance since they suggest that variations in the level of expression of cDK in human prostate cancers might influence their growth properties and response to anti- androgen therapy.__
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2003
- Accession Number
- ADA415662
Entities
People
- I. B. Weinstein
- J. T. Lim
Organizations
- Columbia University