Novel Strategies Targeting Telomere Maintenance for the Treatment and Prevention of Breast Cancer.
Annual rept. 1 Jul 97-30 Jun 98
CALIFORNIA UNIV SAN FRANCISCO
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The goal of this research is to test two new strategies to treat breast cancer, based upon 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 transcriptase 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 strategy, the telomerase RNA template is altered. Progress to date 1 we tested 139 compounds and found three new telomerase inhibitors. 2 We have introduced engineered telomerase RNA genes that direct synthesis of mutated telomeres into breast cancer cells in culture. Next we will determine which telomerase RNA gene sequences cause deleterious telomeric DNA sequences to be synthesized, thereby preventing cell division.
- Medicine and Medical Research