Identification of a novel urokinase receptor splice variant and its prognostic relevance in breast cancer

Thomas Luther, Matthias Kotzsch, Axel Meye, Thomaz Langerholc, Susanne Füssel, Natalie Olbricht, Sybille Albrecht, Detlev Ockert, Bernd Muehlenweg, Katrin Friedrich, Marianne Grosser, Manfred Schmitt, Gustavo Baretton, Viktor Magdolen

Research output: Contribution to journalArticlepeer-review

34 Scopus citations


The cellular receptor for urokinase-type plasminogen activator, uPAR, plays a central role in both cell surface-associated proteolysis and cellular adhesion. In the present study, we systematically searched for splice variants of uPAR mRNA in human cells and tumor tissues by qualitative RT-PCR using specific primers for uPAR exons 1 and 6. Beside the wild-type (wt) uPAR mRNA and the previously described splice variant lacking exon 5 (uPAR-del5), a novel splice variant lacking both exons 4 and 5 (uPAR-del4/5) was found predominantly in various cancer cell lines. To elucidate whether alternatively spliced uPAR mRNA may be translated and post-translationally processed, we generated stably transfected Chinese hamster ovary cells, which harbor expression plasmids of wt uPAR and various uPAR variants including uPAR-del5 and uPAR-del4/5. By ELISA, flow cytofluorometry, and Western blot analysis, we confirmed synthesis and secretion of wt uPAR and the uPAR variants by the use of domain-specific monoclonal antibodies against uPAR. For quantification of uPAR mRNA variants, we established two highly sensitive real-time RT-PCR assays based on LightCycler technology. Study of their expression in a representative set of breast cancer tissues indicated that the novel mRNA variant uPAR-del4/5 was expressed very frequently and independently of uPAR mRNA variants covering exon 4 (uPAR-wt and uPAR-del5). Higher uPAR-del4/5 expression was significantly associated with shorter disease-free survival (p = 0.0004) of breast cancer patients. These results suggest that uPAR-del4/5 mRNA may serve as a novel prognostic marker in breast cancer.

Original languageEnglish
Pages (from-to)705-717
Number of pages13
JournalThrombosis and Haemostasis
Issue number4
StatePublished - 1 Apr 2003


  • Cancer
  • LightCycler technology
  • Splice variants
  • Urokinase receptor
  • mRNA


Dive into the research topics of 'Identification of a novel urokinase receptor splice variant and its prognostic relevance in breast cancer'. Together they form a unique fingerprint.

Cite this