Mammary tumorigenesis induced by fibroblast growth factor receptor 1 requires activation of the epidermal growth factor receptor

Lindsey K. Bade, Jodi E. Goldberg, Hazel A. DeHut, Majken K. Hall, Kaylee Schwertfeger

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Fibroblast growth factor receptor 1 (FGFR1) is an oncoprotein with known involvement in mammary tumorigenesis. To understand how FGFR1 signaling promotes mammary tumorigenesis, an inducible FGFR1 (iFGFR1) system was created previously. Previous studies have demonstrated that upon iFGFR1 activation in vivo, the epidermal growth factor (EGF) ligands amphiregulin (AREG) and epiregulin (EREG) are upregulated. Both AREG and EREG interact with the EGF receptor (EGFR). Here, we investigated whether the FGFR1-induced increase in AREG and EREG expression might coordinately increase EGFR signaling to promote mammary tumorigenesis. Treatment of mouse mammary epithelial cells with either AREG or EREG conferred a greater migratory potential, increased cellular proliferation and increased extracellular regulated kinase 1/2 (ERK1/2) activation. These effects could be blocked with the EGFR-specific inhibitor erlotinib, suggesting that they are EGFR-dependent. In transgenic mice with iFGFR1 under the control of the mouse mammary tumor virus (MMTV) promoter, iFGFR1 activation also led to increased mammary epithelial cell proliferation that was inhibited with erlotinib. Taken together, these data suggest that AREG and EREG mediate tumorigenic phenotypes by activating EGFR signaling, and that the oncogenic potential of FGFR1 requires EGFR activation to promote mammary tumorigenesis.

Original languageEnglish (US)
Pages (from-to)3106-3117
Number of pages12
JournalJournal of Cell Science
Volume124
Issue number18
DOIs
StatePublished - Sep 15 2011

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Receptor, Fibroblast Growth Factor, Type 1
Epidermal Growth Factor Receptor
Carcinogenesis
Breast
Epithelial Cells
Cell Proliferation
Mouse mammary tumor virus
Oncogene Proteins
Epidermal Growth Factor
Carcinogens
Transgenic Mice
Phosphotransferases
Amphiregulin
Epiregulin
Ligands
Phenotype

Keywords

  • Breast cancer
  • EGFR
  • FGFR1
  • Mammary tumor

Cite this

Mammary tumorigenesis induced by fibroblast growth factor receptor 1 requires activation of the epidermal growth factor receptor. / Bade, Lindsey K.; Goldberg, Jodi E.; DeHut, Hazel A.; Hall, Majken K.; Schwertfeger, Kaylee.

In: Journal of Cell Science, Vol. 124, No. 18, 15.09.2011, p. 3106-3117.

Research output: Contribution to journalArticle

Bade, Lindsey K. ; Goldberg, Jodi E. ; DeHut, Hazel A. ; Hall, Majken K. ; Schwertfeger, Kaylee. / Mammary tumorigenesis induced by fibroblast growth factor receptor 1 requires activation of the epidermal growth factor receptor. In: Journal of Cell Science. 2011 ; Vol. 124, No. 18. pp. 3106-3117.
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