CD44 isoform expression follows two 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 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.
Servei d'Anatomia Patològica, Hospital Universitari Germans Trias i Pujol, Barcelona, Spain.
X
X
Roca
J L
JL
Mate
A
A
Ariza
A M
AM
Muñoz-Mármol
C
C
von Uexküll-Güldeband
I
I
Pellicer
J J
JJ
Navas-Palacios
M
M
Isamat
D017398:Alternative Splicing; D001940:Breast / Q000276:immunology*; D001943:Breast Neoplasms / Q000276:immunology*; D003001:Cloning, Molecular; D005260:Female; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics* / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D016133:Polymerase Chain Reaction; D014158:Transcription, Genetic
C112697:CD44v6 antigen; D006023:Glycoproteins; D018960:Hyaluronan Receptors