Insulin activates EGFR by stimulating its interaction with IGF-1R in low-EGFR-expressing TNBC cells

BMB Rep. 2015 Jun;48(6):342-7. doi: 10.5483/bmbrep.2015.48.6.157.

Abstract

The expression of epidermal growth factor receptor (EGFR) is an important diagnostic marker for triple-negative breast cancer (TNBC) cells, which lack three hormonal receptors: estrogen and progesterone receptors as well as epidermal growth factor receptor 2. EGFR transactivation can cause drug resistance in many cancers including TNBC, but the mechanism underlying this phenomenon is poorly defined. Here, we demonstrate that insulin treatment induces EGFR activation by stimulating the interaction of EGFR with insulin-like growth factor receptor 1 (IGF-1R) in the MDA-MB-436 TNBC cell line. These cells express low levels of EGFR, while exhibiting high levels of IGF-1R expression and phosphorylation. Low-EGFRexpressing MDA-MB-436 cells show high sensitivity to insulinstimulated cell growth. Therefore, unexpectedly, insulin stimulation induced EGFR transactivation by regulating its interaction with IGF-1R in low-EGFR-expressing TNBC cells.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Resistance, Neoplasm
  • ErbB Receptors / biosynthesis
  • ErbB Receptors / metabolism*
  • Female
  • Humans
  • Insulin / pharmacology*
  • Receptor, IGF Type 1 / metabolism*
  • Signal Transduction / drug effects
  • Triple Negative Breast Neoplasms / drug therapy*
  • Triple Negative Breast Neoplasms / metabolism*

Substances

  • Insulin
  • EGFR protein, human
  • ErbB Receptors
  • Receptor, IGF Type 1