Metastic Regulation of Differential Splicing of CD44
Abstract
CD44 is a multifunctional adhesion molecule that can undergo extensive alternative RNA splicing to generate multiple isoforms bearing different extracellular domains, a sub set of which have been correlated with metastasis in breast cancer. Three such exons, variable exons 5, 6, and 7, were studied for inclusion in RNA from normal and neoplastic tissues from the mouse, using a recently described system for growth and transplantation of mammary epithelial cell lines. Variable exon 6, but not variable exons 1-5, or 7, was included in CD44 mRNA produced in normal mature mammary gland, indicating that splicing of CD44 is restricted in normal adult mammary tissue. Pregnant or lactating gland expressed variable exon 6, and, at lower levels, variable exons 5 and 7. Patterns of variable exon splicing in the TM2L hyperplasia and the TM40D preneoplasia were similar to that of tissue from pregnant animals, suggesting induction of a normal developmental pattern during hyperplastic growth. Considerable alternative splicing of multiple exons from the v1-v7 region of CD44 was observed in tumors and metastases. These results suggest that hyperplasias and preneoplasias access an alternative processing pattern that is turned on during normal early pregnancy and that this pattern is further accentuated during tumorogenesis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 1997
- Accession Number
- ADA332849
Entities
People
- Susan M. Berget
Organizations
- Baylor College of Medicine