2.50
Hdl Handle:
http://hdl.handle.net/10541/72749
Title:
Aberrant activation of notch signaling in human breast cancer.
Authors:
Stylianou, Spyros; Clarke, Robert B; Brennan, Keith
Abstract:
A 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.
Affiliation:
Wellcome Trust Centre for Cell Matrix Research, Faculty of Life Sciences, University of Manchester, Christie Hospital NHS Trust, Manchester M13 9PT, United Kingdom.
Citation:
Aberrant activation of notch signaling in human breast cancer. 2006, 66 (3):1517-25 Cancer Res.
Journal:
Cancer Research
Issue Date:
1-Feb-2006
URI:
http://hdl.handle.net/10541/72749
DOI:
10.1158/0008-5472.CAN-05-3054
PubMed ID:
16452208
Type:
Article
Language:
en
ISSN:
0008-5472
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorStylianou, Spyros-
dc.contributor.authorClarke, Robert B-
dc.contributor.authorBrennan, Keith-
dc.date.accessioned2009-07-07T12:02:49Z-
dc.date.available2009-07-07T12:02:49Z-
dc.date.issued2006-02-01-
dc.identifier.citationAberrant activation of notch signaling in human breast cancer. 2006, 66 (3):1517-25 Cancer Res.en
dc.identifier.issn0008-5472-
dc.identifier.pmid16452208-
dc.identifier.doi10.1158/0008-5472.CAN-05-3054-
dc.identifier.urihttp://hdl.handle.net/10541/72749-
dc.description.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.en
dc.language.isoenen
dc.subjectBreast Canceren
dc.subjectCell Line Tumouren
dc.subject.meshApoptosis-
dc.subject.meshBreast Neoplasms-
dc.subject.meshCell Line, Tumor-
dc.subject.meshCell Transformation, Neoplastic-
dc.subject.meshEpithelial Cells-
dc.subject.meshHumans-
dc.subject.meshReceptor, Notch1-
dc.subject.meshReceptors, Notch-
dc.subject.meshSignal Transduction-
dc.titleAberrant activation of notch signaling in human breast cancer.en
dc.typeArticleen
dc.contributor.departmentWellcome Trust Centre for Cell Matrix Research, Faculty of Life Sciences, University of Manchester, Christie Hospital NHS Trust, Manchester M13 9PT, United Kingdom.en
dc.identifier.journalCancer Researchen

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