AffiliationWellcome Trust Centre for Cell Matrix Research, Faculty of Life Sciences, University of Manchester, Christie Hospital NHS Trust, Manchester M13 9PT, United Kingdom.
MetadataShow full item record
AbstractA role for Notch signaling in human breast cancer has been suggested by both the development of adenocarcinomas in the murine mammary gland following pathway activation and the loss of Numb expression, a negative regulator of the Notch pathway, in a large proportion of breast carcinomas. However, it is not clear currently whether Notch signaling is frequently activated in breast tumors, and how it causes cellular transformation. Here, we show accumulation of the intracellular domain of Notch1 and hence increased Notch signaling in a wide variety of human breast carcinomas. In addition, we show that increased RBP-Jkappa-dependent Notch signaling is sufficient to transform normal breast epithelial cells and that the mechanism of transformation is most likely through the suppression of apoptosis. More significantly, we show that attenuation of Notch signaling reverts the transformed phenotype of human breast cancer cell lines, suggesting that inhibition of Notch signaling may be a therapeutic strategy for this disease.
CitationAberrant activation of notch signaling in human breast cancer. 2006, 66 (3):1517-25 Cancer Res.
- Loss of negative regulation by Numb over Notch is relevant to human breast carcinogenesis.
- Authors: Pece S, Serresi M, Santolini E, Capra M, Hulleman E, Galimberti V, Zurrida S, Maisonneuve P, Viale G, Di Fiore PP
- Issue date: 2004 Oct 25
- Notch activation induces Akt signaling via an autocrine loop to prevent apoptosis in breast epithelial cells.
- Authors: Meurette O, Stylianou S, Rock R, Collu GM, Gilmore AP, Brennan K
- Issue date: 2009 Jun 15
- Increased Wnt signaling triggers oncogenic conversion of human breast epithelial cells by a Notch-dependent mechanism.
- Authors: Ayyanan A, Civenni G, Ciarloni L, Morel C, Mueller N, Lefort K, Mandinova A, Raffoul W, Fiche M, Dotto GP, Brisken C
- Issue date: 2006 Mar 7
- Notch pathway as candidate therapeutic target in Her2/Neu/ErbB2 receptor-negative breast tumors.
- Authors: Hirose H, Ishii H, Mimori K, Ohta D, Ohkuma M, Tsujii H, Saito T, Sekimoto M, Doki Y, Mori M
- Issue date: 2010 Jan
- Notch activation stimulates migration of breast cancer cells and promotes tumor growth.
- Authors: Bolós V, Mira E, Martínez-Poveda B, Luxán G, Cañamero M, Martínez-A C, Mañes S, de la Pompa JL
- Issue date: 2013