From: HubMed - breast cancer <rssfwd@rssfwd.com>
Date: Wed, Apr 23, 2008 at 9:03 AM
Subject: Protein profiling of human breast tumor cells identifies novel biomarkers associated with molecular subtypes.
To: mesothelioma77@gmail.com
[1]Mol Cell Proteomics. 2008 Apr 20;
Gonçalves A, Charafe-Jauffret E, Bertucci F, Audebert S, Toiron Y, Esterni B, Monville F, Tarpin C, Jacquemier J, Houvenaeghel G, Chabannon C, Extra JM, Viens P, Borg JP, Birnbaum D
Molecular subtypes of breast cancer with relevant biological and clinical features have been recently defined, notably ERBB2-overexpressing, basal-like and luminal-like subtypes. To investigate the ability of mass spectrometry-based proteomic technologies to analyze the molecular complexity of human breast cancer, we performed a SELDI-TOF (surface-enhanced laser/desorption ionization-time of flight)-mass spectrometry (MS) based protein profiling of human breast cell lines (BCLs). Triton soluble proteins from 27 BCLs were incubated with ProteinChip arrays and subjected to SELDI analysis. Unsupervised global hierarchical clustering spontaneously discriminated two groups of BCLs respectively corresponding to "luminal-like" cell lines and to "basal-like" cell lines. These groups of BCLs were also different in terms of estrogen receptor status as well as expression of EGFR and other basal markers. Supervised analysis revealed various protein biomarkers with differential expression in "basal-like" vs "luminal-like" cell lines. We identified two of them as a C-terminal truncated form of ubiquitin and S100A9. In a small series of frozen human breast tumors, we confirmed that C-terminal truncated ubiquitin is observed in primary breast samples and we suggested its higher expression in luminal-like tumors. S100A9 up-regulation was found as part of the transcriptionally-defined basal-like cluster in DNA microarrays analysis of human tumors. S100A9 association with basal subtypes as well as its poor-prognosis value was demonstrated on a series of 547 tumor samples from early breast cancer deposited in a tissue microarray. Our study shows the potential of integrated genomic and proteomic profiling to improve molecular knowledge of complex tumor phenotypes and identify biomarkers with valuable diagnostic or prognostic values.
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Source: http://www.hubmed.org/display.cgi?uids=18426791
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