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

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

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  • 1Department of Gastrointestinal Surgery, Osaka University School of Medicine, Yamadaoka, Osaka, Japan.


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.

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