A soluble dominant negative fibroblast growth factor receptor 4 isoform in human MCF-7 breast cancer cells

Biochem Biophys Res Commun. 2001 Sep 14;287(1):60-5. doi: 10.1006/bbrc.2001.5546.


Fibroblast growth factor receptors (FGFRs) are receptor tyrosine kinases encoded by four closely related genes. FGFR 1, 2, and 3 have a number of isoforms derived by alternative splicing, alternative initiation and exon switching; however, FGFR4 has been reported to encode a single intact receptor with three extracellular immunoglobulin (Ig)-like domains, a transmembrane domain, and a split intracellular kinase. Here we describe a novel C-terminally truncated soluble isoform of FGFR4 expressed by human epithelial breast cancer MCF-7 cells. This isoform results from failure of splicing of intron 4 resulting in an mRNA species that encodes an in-frame premature stop codon. Cells transfected with the corresponding cDNA containing intron 4 express a truncated releasable protein that is identified in conditioned media. This soluble FGFR4 isoform (sFGFR4) abrogates the effect of FGF-1-induced MAPK phosphorylation and PRL gene activation. These findings represent the first description of an endogenous soluble C-terminally truncated FGFR4 isoform with FGF modulatory properties.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Female
  • Fibroblast Growth Factor 1
  • Fibroblast Growth Factor 2 / metabolism
  • Gene Deletion
  • Humans
  • Introns / genetics
  • Mice
  • Molecular Sequence Data
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Protein Isoforms / pharmacology
  • RNA Splicing*
  • Receptor, Fibroblast Growth Factor, Type 4
  • Receptors, Fibroblast Growth Factor / antagonists & inhibitors
  • Receptors, Fibroblast Growth Factor / genetics
  • Receptors, Fibroblast Growth Factor / metabolism*
  • Solubility
  • Tumor Cells, Cultured


  • Protein Isoforms
  • Receptors, Fibroblast Growth Factor
  • Fibroblast Growth Factor 2
  • Fibroblast Growth Factor 1
  • FGFR4 protein, human
  • Fgfr4 protein, mouse
  • Receptor, Fibroblast Growth Factor, Type 4

Associated data

  • GENBANK/AF359241