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dc.contributor.author
Dahl, Edgar
dc.contributor.author
En-Nia, Abdelaziz
dc.contributor.author
Wiesmann, Frank
dc.contributor.author
Krings, Renate
dc.contributor.author
Djudjaj, Sonja
dc.contributor.author
Breuer, Elisabeth
dc.contributor.author
Fuchs, Thomas
dc.contributor.author
Wild, Peter J.
dc.contributor.author
Hartmann, Arndt
dc.contributor.author
Dunn, Sandra E.
dc.contributor.author
Mertens, Peter R.
dc.date.accessioned
2019-06-05T14:41:31Z
dc.date.available
2017-06-09T05:18:04Z
dc.date.available
2019-06-05T14:23:32Z
dc.date.available
2019-06-05T14:41:31Z
dc.date.issued
2009-11-24
dc.identifier.issn
1471-2407
dc.identifier.other
10.1186/1471-2407-9-410
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/21934
dc.identifier.doi
10.3929/ethz-b-000021934
dc.description.abstract
Background Y-box binding protein-1 (YB-1) is the prototypic member of the cold shock protein family that fulfills numerous cellular functions. In the nucleus YB-1 protein orchestrates transcription of proliferation-related genes, whereas in the cytoplasm it associates with mRNA and directs translation. In human tumor entities, such as breast, lung and prostate cancer, cellular YB-1 expression indicates poor clinical outcome, suggesting that YB-1 is an attractive marker to predict patients' prognosis and, potentially, is suitable to individualize treatment protocols. Given these predictive qualities of YB-1 detection we sought to establish a highly specific monoclonal antibody (Mab) for diagnostic testing and its characterization towards outcome prediction (relapse-free and overall survival). Methods Hybridoma cell generation was carried out with recombinant YB-1 protein as immunogen and Mab characterization was performed using immunoblotting and ELISA with recombinant and tagged YB-1 proteins, as well as immunohistochemistry of healthy and breast cancer specimens. Breast tumor tissue array staining results were analyzed for correlations with receptor expression and outcome parameters. Results YB-1-specific Mab F-E2G5 associates with conformational binding epitopes mapping to two domains within the N-terminal half of the protein and detects nuclear YB-1 protein by immunohistochemistry in paraffin-embedded breast cancer tissues. Prognostic evaluation of Mab F-E2G5 was performed by immunohistochemistry of a human breast cancer tissue microarray comprising 179 invasive breast cancers, 8 ductal carcinoma in situ and 37 normal breast tissue samples. Nuclear YB-1 detection in human breast cancer cells was associated with poor overall survival (p = 0.0046). We observed a close correlation between nuclear YB-1 detection and absence of progesterone receptor expression (p = 0.002), indicating that nuclear YB-1 detection marks a specific subgroup of breast cancer. Likely due to limitation of sample size Cox regression models failed to demonstrate significance for nuclear YB-1 detection as independent prognostic marker. Conclusion Monoclonal YB-1 antibody F-E2G5 should be of great value for prospective studies to validate YB-1 as a novel biomarker suitable to optimize breast cancer treatment.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
BioMed Central
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/2.0/
dc.title
Nuclear detection of Y-boxprotein-1 (YB-1) closely associates with progesterone receptor negativity and is a strong adverse survival factor in human breast cancer
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 2.0 Generic
ethz.journal.title
BMC Cancer
ethz.journal.volume
9
en_US
ethz.journal.issue
1
en_US
ethz.journal.abbreviated
BMC cancer (Online)
ethz.pages.start
410
en_US
ethz.size
17 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.nebis
004406129
ethz.publication.place
London
en_US
ethz.publication.status
published
en_US
ethz.date.deposited
2017-06-09T05:18:11Z
ethz.source
ECIT
ethz.identifier.importid
imp59364cf676b4299950
ethz.ecitpid
pub:36720
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-07-18T08:38:59Z
ethz.rosetta.lastUpdated
2019-06-05T14:41:44Z
ethz.rosetta.versionExported
true
ethz.COinS
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