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Breast Cancer Research
Published in: Breast Cancer Research 4/2013

Open Access 01-08-2013 | Research article

Notch activation stimulates migration of breast cancer cells and promotes tumor growth

Authors: Victoria Bolós, Emilia Mira, Beatriz Martínez-Poveda, Guillermo Luxán, Marta Cañamero, Carlos Martínez-A, Santos Mañes, José Luis de la Pompa

Published in: Breast Cancer Research | Issue 4/2013

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Abstract

Introduction

Dysregulated NOTCH receptor activity has been implicated in breast cancer but the mechanisms by which NOTCH contributes to transformation are not yet clear, as it has context-dependent effects on the properties of transformed cells.

Methods

We have used various in vitro and in vivo carcinogenic models to analyze the impact of Notch signaling in the onset and progression of breast tumors.

Results

We found that ectopic expression of the Notch1 intracellular domain (N1ICD) in MCF-7 breast adenocarcinoma cell line caused reduction and delocalization of E-CADHERIN levels and increased migratory and invasive abilities. Notch inhibition in the invasive breast cancer cell line MDA-MB-231 resulted in increased E-CADHERIN expression and a parallel reduction in their invasive capacity. The growth of subcutaneous xenografts produced with MCF-7 cells was boosted after N1ICD induction, in a cell autonomous manner. In vivo Notch1 activation in the mammary gland using the MMTV-Cre driver caused the formation of papillary tumors that showed increased Hes1 and Hey1 expression and delocalized E-cadherin staining.

Conclusions

These results confirm NOTCH1 as a signal triggering epithelial-mesenchymal transition in epithelial cancer cells, which may have implications in tumor dissemination, metastasis and proliferation in vivo. The identification of specific factors interacting with NOTCH signaling could thus be relevant to fully understanding the role of NOTCH in breast neoplasia.
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Metadata
Title
Notch activation stimulates migration of breast cancer cells and promotes tumor growth
Authors
Victoria Bolós
Emilia Mira
Beatriz Martínez-Poveda
Guillermo Luxán
Marta Cañamero
Carlos Martínez-A
Santos Mañes
José Luis de la Pompa
Publication date
01-08-2013
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 4/2013
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr3447

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