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Eph/ephrin profiling in human breast cancer reveals significant associations between expression level and clinical outcome.
- Source :
-
PloS one [PLoS One] 2011; Vol. 6 (9), pp. e24426. Date of Electronic Publication: 2011 Sep 15. - Publication Year :
- 2011
-
Abstract
- Pre-clinical studies provide compelling evidence that Eph family receptor tyrosine kinases (RTKs) and ligands promote cancer growth, neovascularization, invasion, and metastasis. Tumor suppressive roles have also been reported for the receptors, however, creating a potential barrier for clinical application. Determining how these observations relate to clinical outcome is a crucial step for translating the biological and mechanistic data into new molecularly targeted therapies. We investigated eph and ephrin expression in human breast cancer relative to endpoints of overall and/or recurrence-free survival in large microarray datasets. We also investigated protein expression in commercial human breast tissue microarrays (TMA) and Stage I prognostic TMAs linked to recurrence outcome data. We found significant correlations between ephA2, ephA4, ephA7, ephB4, and ephB6 and overall and/or recurrence-free survival in large microarray datasets. Protein expression in TMAs supported these trends. While observed no correlation between ephrin ligand expression and clinical outcome in microarray datasets, ephrin-A1 and EphA2 protein co-expression was significantly associated with recurrence in Stage I prognostic breast cancer TMAs. Our data suggest that several Eph family members are clinically relevant and tractable targets for intervention in human breast cancer. Moreover, profiling Eph receptor expression patterns in the context of relevant ligands and in the context of stage may be valuable in terms of diagnostics and treatment.
- Subjects :
- Breast Neoplasms genetics
Ephrin-A1 genetics
Ephrin-A1 metabolism
Ephrins genetics
Female
Humans
Immunohistochemistry
In Vitro Techniques
Receptor, EphA2 genetics
Receptor, EphA2 metabolism
Receptor, EphA4 genetics
Receptor, EphA4 metabolism
Receptor, EphA7 genetics
Receptor, EphA7 metabolism
Receptor, EphB4 genetics
Receptor, EphB4 metabolism
Receptor, EphB6 genetics
Receptor, EphB6 metabolism
Tissue Array Analysis
Breast Neoplasms metabolism
Ephrins metabolism
Gene Expression Regulation, Neoplastic
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 6
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 21935409
- Full Text :
- https://doi.org/10.1371/journal.pone.0024426