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Updated: Jul 6, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

Involvement of fibroblast growth factor receptor 2 isoform switching in mammary oncogenesis

Jiyoung Y Cha1, Que T Lambert, Gary W Reuther

  • 1Department of Pharmacology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295, USA.

Molecular Cancer Research : MCR
|March 14, 2008
PubMed

Insights

Fibroblast growth factor receptor 2 (FGFR2 IIIb C2) drives epithelial cell growth. Its transformation activity depends on cell type and keratinocyte growth factor signaling, revealing context-specific oncogenic mechanisms.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Fibroblast growth factor receptor 2 (FGFR2) has splice variants, including FGFR2 IIIb and FGFR2 IIIc.
  • FGFR2 IIIb is epithelial-specific, while FGFR2 IIIc is mesenchymal-specific.
  • The oncogenic role of FGFR2 IIIb in epithelial cells requires further investigation.

Purpose of the Study:

  • To investigate the transforming activity of the FGFR2 IIIb C2 splice variant in epithelial cells.
  • To compare the transforming potential of FGFR2 IIIb C2 in different cell contexts (epithelial vs. fibroblast).
  • To elucidate the mechanisms underlying FGFR2 IIIb C2-mediated transformation, including ligand dependency.

Main Methods:

  • Screening for activated oncogenes in breast carcinoma cell lines.
  • Comparing the transforming effects of FGFR2 IIIb C2 in RIE-1 intestinal cells, mammary epithelial cells, and NIH 3T3 fibroblasts.
  • Analyzing Ras activation and cyclin D1 expression.
  • Investigating the role of keratinocyte growth factor (KGF) in FGFR2 IIIb C2 transformation.

Main Results:

  • FGFR2 IIIb C2 expression was identified in breast carcinoma cell lines.
  • FGFR2 IIIb C2 induced growth transformation in epithelial cells and morphologic transformation in NIH 3T3 fibroblasts.
  • Transformation in NIH 3T3 cells involved Ras activation and cyclin D1 upregulation, while RIE-1 cell transformation was KGF-dependent.
  • Both ligand-independent and ligand-dependent mechanisms contribute to FGFR2 IIIb C2 transformation.

Conclusions:

  • FGFR2 IIIb C2 exhibits cell context-distinct transforming activities.
  • Mechanisms of FGFR2 IIIb C2 transformation involve both intrinsic signaling and stromal-derived KGF.
  • Findings highlight the complex role of FGFR2 splice variants in cancer development.

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