Epidermal growth factor receptor plays a significant role in hepatocyte growth factor mediated biological responses in mammary epithelial cells

Alyssa R. Bonine-Summers, Mary E. Aakre, Kimberly A. Brown, Carlos L. Arteaga, Jennifer A. Pietenpol, Harold L. Moses, Nikki Cheng

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

Breast cancers often have deregulated hepatocyte growth factor (HGF) and c-Met signaling that results in increased tumor growth and invasion. Elucidating the mechanism responsible for HGF/c-Met action in breast cancer progression has been difficult as c-Met communicates with a number of secondary receptors that can lead to various pathological outcomes. Understanding how these secondary receptors facilitate HGF/c-Met cellular responses will aid in the development of better therapeutic treatment options for breast cancer patients with elevated HGF signaling. In the present study it was shown that the epidermal growth factor receptor (EGFR) plays a significant role in HGF/c-Met mediated biological activities indicative of advanced tumor pathology, including enhanced proliferation and invasion. The clinically relevant EGFR inhibitor gefitinib was used to determine the role of EGFR in HGF-induced proliferation and motility in several mammary carcinoma cells including PyVmT, MDA-MB-231 and 4T1. Our analyses indicated that EGFR inhibition significantly blocked HGF activation of c-Met and EGFR and that inhibition of these pathways mitigated HGF induced proliferation and motility. The data indicate that this inhibition was not through a direct effect of gefitinib on c-Met, but that EGFR is necessary for c-Met activation in the assays performed. These results provide a novel mechanism of action for EGFR as a mediator of HGF signaling thereby linking EGFR to the oncogenic potential of c-Met in mammary carcinomas cells.

Original languageEnglish (US)
Pages (from-to)561-570
Number of pages10
JournalCancer Biology and Therapy
Volume6
Issue number4
DOIs
StatePublished - Apr 2007

Keywords

  • Cross-talk
  • Epidermal growth factor receptor
  • Growth and breast cancer
  • Hepatocyte growth factor
  • Motility
  • Signaling
  • Therapy
  • c-Met

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

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