Intercellular Communication and Chemoprevention of Prostate Cancer by Analogs of Vitamin A and D
Abstract
Though the natural and synthetic analogs of vitamin A and D are used as chemopreventive agents, their use in clinical trials has been hampered due to toxic effects. We have identified 2 genes that regulate the invasiveness of prostate cancer (PCA) cells. They code for proteins called connexins which assemble to form specialized structures called gap junctions that allow the exchange of small molecules between cells - a phenomenon called intercellular communication. Our studies show loss of connexins in advanced PCA, and reintroduction of connexins corrects the invasiveness of PCA cells. Our studies further show that treatment of human PCA cell lines with vitamin A and D analogs enhances gap junction formation. We have proposed that strategies designed to direct chemopreventive agents to restore defective intercellular communication in prostate tumors may prove to be more effective. To reduce the side effects associated with vitamin A and D analogs, we have proposed experiments that will help us optimize concentrations of these agents, either alone or in combination, that will be the least toxic and most effective in restoring defective communication in PCA cells. We anticipate that these optimized concentrations will also be the most effective in the chemoprevention of PCA.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2002
- Accession Number
- ADA404664
Entities
People
- Parmender P Mehta
Organizations
- University of Nebraska Medical Center