The Role of the Polypyrimidine Tract Binding Protein on CD44 Splicing in Breast Cancer
Abstract
The cytogenetic and nuclear changes during breast tumor progression have been well documented, but the causes of these alterations are poorly understood. Changes in estrogen receptor status, gain in metastatic potential, accumulation of PNCs, and differential splicing of genes are changes seen in breast cancer cells during tumor progression. A strong connection between the splicing machinery and these subtle, significant, changes in gene expression have yet to be documented. Likely candidates are the alternative splicing factors, most notably the Polypyrimidine Tract Binding Protein (PTB). PTB is a known repressor of exon definition. During breast cancer progression, we believe, PTB's ability to repress exons is altered. To understand the changes in PTB function as cancer cells de-differentiate, an understanding of PTB mechanism must be attained. We are using the regulation of FClFR2 exon In, as a model system to study PTB mediated repression. We have mapped pTB binding sites and through the use of heterologous recruitment and RNAi mediated pTB depletion have clearly demonstrated PTB's function in the exon 11th repression. Furthermore, we have defined the cell-type specific cis-regulatory elements responsible for overcoming PTB repressive effects and have identified a potential trans-acting factor, Fox-1, that has been reported to antagonize FTB.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2003
- Accession Number
- ADA424409
Entities
People
- Andrew Baraniak
- Mariano A. Garcia-blanco
Organizations
- Duke University Hospital