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 journalArticle

29 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)35-43
Number of pages9
JournalOncology reports
Volume23
Issue number1
DOIs
Publication statusPublished - Feb 11 2010

Fingerprint

ErbB-2 Receptor
Breast Neoplasms
Neoplasms
Therapeutics
Mutagens
Cell Death
Immunohistochemistry
Radiation
Growth

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Notch pathway as candidate therapeutic target in Her2/Neu/ErbB2 receptor-negative breast tumors. / Hirose, Hajime; Ishii, Hideshi; Mimori, Koshi; Ohta, Daisuke; Ohkuma, Masahisa; Tsujii, Hirohiko; Saito, Toshiyuki; Sekimoto, Mitsugu; Doki, Yuichiro; Mori, Masaki.

In: Oncology reports, Vol. 23, No. 1, 11.02.2010, p. 35-43.

Research output: Contribution to journalArticle

Hirose, H, Ishii, H, Mimori, K, Ohta, D, Ohkuma, M, Tsujii, H, Saito, T, Sekimoto, M, Doki, Y & Mori, M 2010, 'Notch pathway as candidate therapeutic target in Her2/Neu/ErbB2 receptor-negative breast tumors', Oncology reports, vol. 23, no. 1, pp. 35-43. https://doi.org/10.3892/or-00000603
Hirose, Hajime ; Ishii, Hideshi ; Mimori, Koshi ; Ohta, Daisuke ; Ohkuma, Masahisa ; Tsujii, Hirohiko ; Saito, Toshiyuki ; Sekimoto, Mitsugu ; Doki, Yuichiro ; Mori, Masaki. / Notch pathway as candidate therapeutic target in Her2/Neu/ErbB2 receptor-negative breast tumors. In: Oncology reports. 2010 ; Vol. 23, No. 1. pp. 35-43.
@article{8266cc89c6da442182a928f4528c51be,
title = "Notch pathway as candidate therapeutic target in Her2/Neu/ErbB2 receptor-negative breast tumors",
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.",
author = "Hajime Hirose and Hideshi Ishii and Koshi Mimori and Daisuke Ohta and Masahisa Ohkuma and Hirohiko Tsujii and Toshiyuki Saito and Mitsugu Sekimoto and Yuichiro Doki and Masaki Mori",
year = "2010",
month = "2",
day = "11",
doi = "10.3892/or-00000603",
language = "English",
volume = "23",
pages = "35--43",
journal = "Oncology Reports",
issn = "1021-335X",
publisher = "Spandidos Publications",
number = "1",

}

TY - JOUR

T1 - Notch pathway as candidate therapeutic target in Her2/Neu/ErbB2 receptor-negative breast tumors

AU - Hirose, Hajime

AU - Ishii, Hideshi

AU - Mimori, Koshi

AU - Ohta, Daisuke

AU - Ohkuma, Masahisa

AU - Tsujii, Hirohiko

AU - Saito, Toshiyuki

AU - Sekimoto, Mitsugu

AU - Doki, Yuichiro

AU - Mori, Masaki

PY - 2010/2/11

Y1 - 2010/2/11

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=76049096035&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=76049096035&partnerID=8YFLogxK

U2 - 10.3892/or-00000603

DO - 10.3892/or-00000603

M3 - Article

C2 - 19956862

AN - SCOPUS:76049096035

VL - 23

SP - 35

EP - 43

JO - Oncology Reports

JF - Oncology Reports

SN - 1021-335X

IS - 1

ER -