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

  • Authors:
    • Hajime Hirose
    • Hideshi Ishii
    • Koshi Mimori
    • Daisuke Ohta
    • Masahisa Ohkuma
    • Hirohiko Tsujii
    • Toshiyuki Saito
    • Mitsugu Sekimoto
    • Yuichiro Doki
    • Masaki Mori
  • View Affiliations

  • Published online on: January 1, 2010     https://doi.org/10.3892/or_00000603
  • Pages: 35-43
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Abstract

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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January 2010
Volume 23 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Hirose H, Ishii H, Mimori K, Ohta D, Ohkuma M, Tsujii H, Saito T, Sekimoto M, Doki Y, Mori M, Mori M, et al: Notch pathway as candidate therapeutic target in Her2/Neu/ErbB2 receptor-negative breast tumors. Oncol Rep 23: 35-43, 2010
APA
Hirose, H., Ishii, H., Mimori, K., Ohta, D., Ohkuma, M., Tsujii, H. ... Mori, M. (2010). Notch pathway as candidate therapeutic target in Her2/Neu/ErbB2 receptor-negative breast tumors. Oncology Reports, 23, 35-43. https://doi.org/10.3892/or_00000603
MLA
Hirose, H., Ishii, H., Mimori, K., Ohta, D., Ohkuma, M., Tsujii, H., Saito, T., Sekimoto, M., Doki, Y., Mori, M."Notch pathway as candidate therapeutic target in Her2/Neu/ErbB2 receptor-negative breast tumors". Oncology Reports 23.1 (2010): 35-43.
Chicago
Hirose, H., Ishii, H., Mimori, K., Ohta, D., Ohkuma, M., Tsujii, H., Saito, T., Sekimoto, M., Doki, Y., Mori, M."Notch pathway as candidate therapeutic target in Her2/Neu/ErbB2 receptor-negative breast tumors". Oncology Reports 23, no. 1 (2010): 35-43. https://doi.org/10.3892/or_00000603