Metastatic Regulation of Differential Splicing of CD44
Abstract
Alternative splicing of pre-mRNAs has the capacity to create many different gene products from a single transcription unit. It has recently become apparent that alternative processing is altered during cancer. Our project studies the alternative processing of a gene, CD44, that is both massively alternatively processed and in which alterations in alternative processing have been linked to cancer. In the past progress period we have concentrated on identifying and characterizing the factors that bind to two of the alternative exons in the CD44 gene and their expression patterns in a murine model of mammary tumorigenesis. We have discovered that three splicing factors -- human Tra2alpha, SRp20, and SRp75 affect the inclusion of CD44 alternative exons 4 and 5 in vivo. In contrast other known splicing enhancer proteins such as SRp55, ASF/SF2, 9G8, and SC35 have no ability to enhance CD44 splicing. Tra2alpha is not expressed in mature gland from virgin female mice but is induced in both pregnancy and preneoplasias. High levels of Tra2alpha were detected in mammary tumors and their metastases, tissues in which the inclusion of CD44 variable exons 4 and 5 increase, suggesting a potential role for Tra2alpha in the increase of CD44 variable splicing observed during cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 1999
- Accession Number
- ADA377159
Entities
People
- Susan M. Berget
Organizations
- Baylor College of Medicine