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.
- 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
- A study on Notch signaling in human breast cancer.
- Authors: Zang S, Ji Ch, Qu X, Dong X, Ma D, Ye J, Ma R, Dai J, Guo D
- Issue date: 2007
- 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
- Cooperation of Notch and Ras/MAPK signaling pathways in human breast carcinogenesis.
- Authors: Mittal S, Subramanyam D, Dey D, Kumar RV, Rangarajan A
- Issue date: 2009 Dec 23
- Epithelial transformation by KLF4 requires Notch1 but not canonical Notch1 signaling.
- Authors: Liu Z, Teng L, Bailey SK, Frost AR, Bland KI, LoBuglio AF, Ruppert JM, Lobo-Ruppert SM
- Issue date: 2009 Oct