Role of the Telomerase Inhibitor PinX1 in Breast Cancer
Abstract
Aim 1 is to determine if PinX1 levels are altered in breast cancer tissues and cell lines. We have currently identified several breast cancer samples with reduced PinX1 levels and at least two with barely detectable expression when compared to normal breast tissue. Our screen to identify mutations in the PINX1 gene in breast cancer samples (Aim 2) has thus far identified four C-terminal mutations which are currently being tested for functional significance. To define the region of PinX1 responsible for telomerase inhibition (Aim 3), we have generated a series of truncated proteins and tested their ability to bind to and inhibit telomerase. We have further defined the residues responsible for PinX1 activity in telomerase inhibition and tumorigenesis by generating PinX1 mutant proteins harboring single and multiple amino acid substitutions of conserved residues within the minimal TID and of breast cancer genetic alterations identified in our screen. Our results indicate that the mutation of several conserved residues are sufficient to disrupt hTert binding and telomerase inhibition and that the mutations identified in our screen disrupt telomerase activity slightly and may be crucial in the development of cancer. These results reflect substantial progress toward determining the mechanism and role of PinX1 in breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2006
- Accession Number
- ADA462345
Entities
People
- Christina Soohoo
Organizations
- Beth Israel Deaconess Medical Center