Metastatic Regulation of Differential Splicing of CD44
Abstract
Alternative mRNA splicing is a major step in gene expression used to produce different forms of a protein for specific cellular purposes. The process is normally carefully regulated to limit production of different mRNA isoforms to only appropriate tissues. Cancer, however, alters splicing regulation and causes the appearance of forms of mRNA and their protein products not normally present in a cell. The cell surface receptor CD44, is a protein that undergoes extensive alternative processing and whose processing alters in both breast cancer tumors and their metastases. We have been investigating this splicing of several alternative exons within the CD44 gene to understand how the splicing of these exons is regulated and how that splicing alters during tumorigenesis and metastasis. We have observed exon sequences and RNA-binding proteins that are required for recognition and splicing of these exons. The three proteins are the SR splicing factor human Tra 2 the y-box protein YB 1, and the ATP-dependent DEAD-box RNA helicase p72. These proteins may be significant for exon recognition because raising the in vivo concentration of and one protein enhances CD44 alternative splicing. More importantly the levels of Tra2 and p72 increase in mammary tumors and their metastases making them candidate factors responsible for altering CD44 splicing during tumorigenesis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2001
- Accession Number
- ADB281663
Entities
People
- Susan M. Berget
Organizations
- Baylor College of Medicine