2026-04-28T21:35:05Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/77722024-09-27T09:29:53Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Bolos, Victoria author Mira, Emilia author Martinez-Poveda, Beatriz author Luxan, Guillermo author Cañamero, Marta author Martínez-A, Carlos author Mañes, Santos author de la Pompa, Jose Luis author 2013 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. Breast Cancer Res. 2013; 15(4):R54 1465-542X http://hdl.handle.net/20.500.12105/7772 23826634 10.1186/bcr3447 1465-542X Breast cancer research : BCR Notch activation stimulates migration of breast cancer cells and promotes tumor growth