Cross-talk between Notch and EGFR signaling in human breast cancer cells

Cancer Invest. 2009 Jun;27(5):533-40. doi: 10.1080/07357900802563036.

Abstract

Notch and epidermal growth factor receptor (EGFR) signaling play critical roles in cell proliferation, differentiation, and apoptosis, and thereby may contribute to the development of breast cancer. We constitutively overexpressed active Notch1 in human breast cancer cells to explore the consequences of Notch1 signaling on cell growth and to investigate the underlying molecular mechanisms. We found that EGFR expression was increased. Then, using EGFR inhibitor, we found it exhibited an inhibitory role on human breast cancer cells. Overexpression of Notch1 could reverse EGFR inhibitor-induced cell toxicity, suggesting that Notch and EGFR signaling may be positively cross-linked in human breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Blotting, Western
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Cell Cycle / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism*
  • Female
  • Gefitinib
  • Humans
  • Kidney / cytology
  • Kidney / drug effects
  • Kidney / metabolism
  • Protein Kinase Inhibitors / pharmacology
  • Quinazolines / pharmacology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptor, Notch1 / genetics
  • Receptor, Notch1 / metabolism*
  • Retroviridae / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction*

Substances

  • NOTCH1 protein, human
  • Protein Kinase Inhibitors
  • Quinazolines
  • RNA, Messenger
  • Receptor, Notch1
  • EGFR protein, human
  • ErbB Receptors
  • Gefitinib