The Expression and Regulation of the Cell Adhesion Molecule CD44 in Human Breast Cancer.
Annual rept. 1 Aug 94-31 Jul 95,
PITTSBURGH UNIV PA
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The polymorphic cell adhesion molecule CD44 is encoded by a complex gene and undergoes extensive alternative splicing. Differential regulation of CD44 alternative splicing has been implicated in human tumorigenesis, and differences in variant isoform expression have been detected in normal versus tumor breast tissue. Our prospective analysis of 99 human breast samples by RT-PCR and Southern blotting reveals that approximately half of the tumor samples express qualitatively more CD44 than their normal counterparts. Our study also reveals that some normal breast specimens express CD44 variant isoforms. A novel CD44 isoform generated by a unique splicing event has been cloned from BT-20 breast tumor cells and may represent a breast cell specific variant. To identify the cis- and trans-acting signals involved in CD44 splicing, newly constructed CD44 minigenes have been transfected into breast cell lines which will be fused to form transient heterokaryons. SR protein splicing factors have been purified and detected in breast cell lines, and their role in CD44 alternative splicing will be examined.
- Anatomy and Physiology