The Role of the Polypyrimidine Tract Binding Protein on CD44 Alternative Splicing in Breast Cancer
Abstract
The cytogenetic and nuclear changes that occur during tumor progression in the breast have been well documented, but the causes of these alterations are poorly understood. Changes in estrogen receptor status, loss of responsiveness to conventional chemotherapy, gain in metastatic potential, accumulation of PNCs, and differential splicing of CD44 pre-mRNA are examples of changes seen in breast cancer cells during tumor progression. Thus far, a strong connection between the splicing machinery and these subtle, yet significant, changes in gene expression has 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. We believe that modification of PTB's ability to repress exons, possibly in CD44, to be occurring as breast cells as well as many other cancers. We are attempting to design molecular assays that will display the significance of PTB on the alternative splicing of CD44. We are using a GFP based minigene to define cis elements required for regulation. Thus far, we have been able to demonstrate the versatility of this reporter in living cells and recapitulate PTB-mediated repression on the exon IIIb of FGF-R2, which is another pre-mRNA known to be regulated by PTB and whose regulation is lost during tumor progression.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2001
- Accession Number
- ADA396499
Entities
People
- Eric J. Wagner
- Mariano A. Garcia-blanco
Organizations
- Duke University Hospital