Alternative inclusion of fibroblast growth factor receptor 2 exon IIIc in Dunning prostrate tumors reveals unexpected epithelial mesenchymal plasticity

Sebastian Oltean, Brian S. Sorg, Todd Albrecht, Vivian I. Bonano, Robert M. Brazas, Mark W. Dewhirst, Mariano A. Garcia-Blanco

Research output: Contribution to journalArticle

81 Scopus citations

Abstract

In epithelial cells, alternative splicing of fibroblast growth factor receptor 2 (FGFR2) transcripts leads to the expression of the FGFR2(IIIb) isoform, whereas in mesenchymal cells, the same process results in the synthesis of FGFR2(IIIc). Expression of the FGFR2(IIIc) isoform during prostate tumor progression suggests a disruption of the epithelial character of these tumors. To visualize the use of FGFR2 exon IIIc in prostate AT3 tumors in syngeneic rats, we constructed minigene constructs that report on alternative splicing. Imaging these alternative splicing decisions revealed unexpected mesenchymal-epithelial transitions in these primary tumors. These transitions were observed more frequently where tumor cells were in contact with stroma. Indeed, these transitions were frequently observed among lung micrometastases in the organ parenchyma and immediately adjacent to blood vessels. Our data suggest an unforeseen relationship between epithelial mesenchymal plasticity and malignant fitness.

Original languageEnglish (US)
Pages (from-to)14116-14121
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number38
DOIs
StatePublished - Sep 19 2006
Externally publishedYes

Keywords

  • Alternative splicing
  • Mesenchymal-epithelial transitions
  • Tumor plasticity

ASJC Scopus subject areas

  • General

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