Targeted Therapy of Human Breast Cancer by 2-5A-Antisense Directed Against Telomerase RNA
Abstract
In most normal cells DNA is lost from the ends of the chromosomes (telomeres) at each cell cycle. In rapidly growing tumor cells this eventually results in chromosome instability and cell death. To overcome this problem most cancer cells re-express the telomerase enzyme which prevents telomere erosion. To establish whether expressing telomerase is essential to maintain the malignant phenotype in these tumor cells, we have used an anti sense oligonucleotide approach targeting the RNA component of the telomerase enzyme. The oligonucleotides used carry a 2-5A moiety which activates RNAseL to selectively destroy the target RNA. Using this system we have shown that targeting telomerase causes rapid cell death in several different breast cancer cell lines in vitro. This cell death is not seen when the cells are treated with control oligos carrying mismatches in the target sequence. Cell death is due to apoptosis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1999
- Accession Number
- ADA384610
Entities
People
- John K. Cowell