CD44 ISOFORM EXPRESSION FOLLOWS 2 ALTERNATIVE SPLICING PATHWAYS IN BREAST-TISSUE

The repertoire of distinct CD44 protein isoforms is generated by means of alternative pre-mRNA splicing of 10 variable exons located in the central region of the CD44 gene. We have used human breast ductal carc inoma as a model to identify two alternative splicing pathways of the CD44 pre-mRNA variable region that account for the generation of all o f the CD44 isoforms described in breast tissue. An alternative splicin g pathway that reflects inclusion of variable exons in a gradual 3'-to -5' fashion is evidenced in breast ductal carcinoma and its lymph node metastases. This pathway is compatible with a mechanism that generate s the standard form of CD44 (devoid of variable exons) and is distingu ishable from an alternative splicing pathway that involves exclusively variant exon 3 and is observable in both normal and carcinoma breast tissue. We show that both pathways are detectable in the same cell typ e in the breast and provide a speculative model by which these splicin g routes could take place.