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(American Journal of Pathology. 1998;153:183-190.)
© 1998 American Society for Investigative Pathology

Regular Articles

CD44 Isoform Expression Follows Two Alternative Splicing Pathways in Breast Tissue

Xavier Roca* , José L. Mate* , Aurelio Ariza* , Ana M. Muñoz-Mármol{dagger} , Claudia von Uexküll-Güldeband{dagger} , Inmaculada Pellicer* , José J. Navas-Palacios* and Marcos Isamat{dagger}

From the Servei d'Anatomia Patològica,* Hospital Universitari Germans Trias i Pujol, and the Fundación Echevarne,{dagger} Barcelona, Spain

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 carcinoma as a model to identify two alternative splicing pathways of the CD44 pre-mRNA variable region that account for the generation of all of the CD44 isoforms described in breast tissue. An alternative splicing 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 generates the standard form of CD44 (devoid of variable exons) and is distinguishable 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 type in the breast and provide a speculative model by which these splicing routes could take place.




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