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

Hajime Hirose, Hideshi Ishii, Koshi Mimori, Daisuke Ohta, Masahisa Ohkuma, Hirohiko Tsujii, Toshiyuki Saito, Mitsugu Sekimoto, Yuichiro Doki, Masaki Mori

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)35-43
Number of pages9
JournalOncology reports
Issue number1
Publication statusPublished - 2010

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


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