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

作者：Hirose Hajime; Ishii Hideshi; Mimori Koshi; Ohta Daisuke; Ohkuma Masahisa; Tsujii Hirohiko; Saito Toshiyuki; Sekimoto Mitsugu; Doki Yuichiro; Mori Masaki^*

来源：Oncology Reports, 2010, 23(1): 35-43.

DOI：10.3892/or_00000603

• Notch
• ErbB2 receptor
• breast tumors

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.

• 出版日期2010-1