Regulation of hTERT Expression and Function in Newly Immortalized p53(+) Human Mammary Epithelial Cell Lines
Abstract
Telomerase is reactivated in almost all human breast cancers; loss of telomeric protection usually leads to genomic instability. This proposal is to study telomerase reactivation and telomere protection in newly immortalized human mammary epithelial cells (HMEC) that retain wild type p53 function and to determine if these cells may be especially sensitive to therapies that target telomerase activity and telomere protection. Prior work showed that p53 can suppress most but not all telomerase expression in newly immortal p53+ HMEC lines until telomeres become extremely short when an unknown mechanism (termed conversion) relieves this repression. We hypothesized that the observed upregulation of cyclin-dependent kinase inhibitor p57 might protect cells with critically shortened telomeres by inhibiting growth until there is sufficient telomerase to protect the telomeric ends. However in the past year we observed that inhibition of p57 produced a result similar to that seen when telomerase was inhibited and did not lead to mitotic failure. We are currently addressing the questions: (1) What is the role of upregulated p57 during conversion; (2) Can inhibition of telomerase and/or p57 efficiently kill these cells; (3) How does p53 regulate telomerase activity in newly immortal HMEC lines.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2006
- Accession Number
- ADA457687
Entities
People
- Martha R Stampfer
Organizations
- University of California, Berkeley