Metastic Regulation of Differential splicing of CD44.
Abstract
CD44 is a multi-functional adhesion molecule that can undergo alternative RNA splicing to generate multiple isoforms bearing different extracellular domains, a sub-set of which have been correlated with metastasis in breast cancer. Using a mouse model of mammary carcinogenesis we have observed that CD44 variable splicing alters during both normal breast development and mammary cancer. Pre-neoplasias, a tissue difficult to assay in humans exhibited alternative processing patterns similar to that in pregnant and lactating breast. The transition from pre-neoplasia to neoplasia was accompanied by strong increases in CD44 variable splicing. During the same progressions, alternative splicing factors expression changed. Co-transfection of some of these splicing factors along with a CD44 reported gene containing variable exons 4 and 5 demonstrated that CD44 splicing could be altered by these factors. Both positive and negative factors for CD44 splicing were identified. The concentration of both altered during neoplasia. These results suggest that alterations in splicing factors during early stages of breast cancer can have marked effects on RNA splicing to produce radically different proteins with different properties than those in normal cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 1998
- Accession Number
- ADA355331
Entities
People
- Susan M. Berget
Organizations
- Baylor College of Medicine