Metastic Regulation of Differential Splicing of CD44
Annual rept. 15 Jul 1999-14 Jul 2000
BAYLOR COLL OF MEDICINE HOUSTON TX
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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 mRNAs and their protein products not normally present in a cell. The cell surface receptor CD4, 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 sequences within two alternatively recognized exons that are the binding sites for two important RNA-binding proteins - human Tra 2 and the y-box protein YB 1. Both proteins bind these exon sequences. This binding may be significant for exon recognition because raising the in vivo concentration of either protein enhances CD44 alternative splicing. More importantly the levels of both proteins increase in mammary tumors and their metastases making them candidate factors responsible for altering CD44 splicing during tumorigenesis.
- Anatomy and Physiology
- Medicine and Medical Research