Notch pathway as candidate therapeutic target in Her2/Neu/ErbB2 receptor-negative breast tumors

Oncol Rep. 2010 Jan;23(1):35-43.


Whereas the Her2/neu/erbB2 receptor (Her2) could be a molecular target of the receptor-positive breast cancer, the therapeutic targets of Her2-negative cancer largely remain to be established. The expression of Her2 was evaluated in 48 primary breast cancer tumors by immunohistochemistry. The identified Notch pathway was studied in genotoxin-dependent suppression of breast cancer-initiating cell growth. Immunohistochemical assessment of Her2-negative tumors revealed significant association with overexpression of Notch1 and Notch3. Knockdown of Notch pathway resulted in sensitization of breast cancer cells to deionizing radiation, leading to cell death; the effect was more significant in stem marker CD44+ than in CD44- cells, and more profound in the Her2-negative than in positive cancer cells. The present study indicates that inhibition of Notch signaling could antagonize survival signal of Her2-negative breast cancer-initiating cells carrying genomic damage, and suggests that targeted suppression of the Notch pathway may give the rationale for sensitizing Her2-negative cancer-initiating cells to a therapeutic approach.

MeSH terms

  • Adult
  • Aged
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / therapy*
  • Cell Line, Tumor
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Hyaluronan Receptors / biosynthesis
  • Immunohistochemistry / methods
  • Middle Aged
  • Models, Biological
  • RNA, Small Interfering / metabolism
  • Receptor, ErbB-2 / biosynthesis*
  • Receptors, Notch / metabolism*
  • Signal Transduction


  • Hyaluronan Receptors
  • RNA, Small Interfering
  • Receptors, Notch
  • Receptor, ErbB-2