Novel Strategies Targeting Telomere Maintenance for the Treatment and Prevention of Breast Cancer
Abstract
The goal of this research is to test two new strategies to treat breast cancer, based on altering telomerase action. The ribonucleoprotein telomerase synthesizes telomeric DNA by copying a template RNA sequence within the essential RNA of telomerase. Without telomerase, as cells divide, their telomeres shrink and eventually the cells cease dividing. Telomerase activity is commonly found in human breast cancer cells but not in many normal cells. First, inhibitors of telomerase will be used to prevent telomerase from maintaining telomeres. We previously found that we can inhibit telomerase from breast cancer cell lines with reverse transcripts inhibitors. The second novel (gene therapy) strategy will direct telomerase to synthesize "toxic" telomeric DNA sequences in breast cancer cells, thereby quickly causing them to cease dividing. In this second strategy, the telomerase RNA template is altered. Progress to date: 1) we tested 139 compounds and found three new telomerase specific inhibitors. 2) We have introduced engineered telomerase RNA genes that direct synthesis of mutated telomeres into breast cancer cells in culture. We determined that these telomerase RNA gene sequences caused deleterious telomeric DNA synthesis, thereby interfering with cell proliferation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1999
- Accession Number
- ADA373912
Entities
People
- Elizabeth H. Blackburn
Organizations
- University of California, San Francisco