Isolation of Factors that Disrupt Critical Protein
Abstract
One of the earliest events associated with the multistage pathogenesis of breast cancer is the activation of telomerase. Telomerase is a reverse transcriptase that elongates the ends of chromosomes and is required to prevent replicative senescence in proliferative cells. While not expressed in most adult human tissues, high levels of telomerase activity are present in most cancers. Ectopic expression of telomerase in many primary cell cultures is sufficient to bypass normal senescence. Cellular senescence can act as a terminal growth-control checkpoint, preventing the progression of pre-cancerous cells to malignancy. Blockade of telomerase activity in breast neoplasias should reintroduce this checkpoint, resulting in replication-dependent senescence of proliferating cells. Therefore, telomerase antagonists could potentially control growth and metastasis of residual cancer cells after surgery and chemotherapy. We are using two strategies to produce telomerase antagonists: 1) isolation of peptide aptamers that disrupt critical protein/protein interactions in the telomerase holoenzyme complex, and 2) development of an siRNA expression system to silence expression of hTERT and hTR RNAs.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2002
- Accession Number
- ADA405582
Entities
People
- Michael A. White
Organizations
- University of Texas at Dallas