Comprehensive proteomic analysis of breast cancer cell membranes reveals unique proteins with potential roles in clinical cancer

Paul J. Adam, Robert Boyd, Kerry L. Tyson, Graham C. Fletcher, Alasdair Stamps, Lindsey Hudson, Helen R. Poyser, Nick Redpath, Matthew Griffiths, Graham Steers, Adrian L. Harris, Sonal Patel, Joanne Berry, Julie A. Loader, R. Reid Townsend, Laurent Daviet, Pierre Legrain, Raj Parekh, Jonathan A. Terrett

Research output: Contribution to journalArticle

176 Scopus citations

Abstract

Proteins associated with cancer cell plasma membranes are rich in known drug and antibody targets as well as other proteins known to play key roles in the abnormal signal transduction processes required for carcinogenesis. We describe here a proteomics process that comprehensively annotates the protein content of breast tumor cell membranes and defines the clinical relevance of such proteins. Tumor-derived cell lines were used to ensure an enrichment for cancer cell-specific plasma membrane proteins because it is difficult to purify cancer cells and then obtain good membrane preparations from clinical material. Multiple cell lines with different molecular pathologies were used to represent the clinical heterogeneity of breast cancer. Peptide tandem mass spectra were searched against a comprehensive data base containing known and conceptual proteins derived from many public data bases including the draft human genome sequences. This plasma membrane-enriched proteome analysis created a data base of more than 500 breast cancer cell line proteins, 27% of which were of unknown function. The value of our approach is demonstrated by further detailed analyses of three previously uncharacterized proteins whose clinical relevance has been defined by their unique cancer expression profiles and the identification of protein-binding partners that elucidate potential functionality in cancer.

Original languageEnglish
Pages (from-to)6482-6489
Number of pages8
JournalJournal of Biological Chemistry
Volume278
Issue number8
DOIs
StatePublished - Feb 21 2003
Externally publishedYes

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    Adam, P. J., Boyd, R., Tyson, K. L., Fletcher, G. C., Stamps, A., Hudson, L., Poyser, H. R., Redpath, N., Griffiths, M., Steers, G., Harris, A. L., Patel, S., Berry, J., Loader, J. A., Townsend, R. R., Daviet, L., Legrain, P., Parekh, R., & Terrett, J. A. (2003). Comprehensive proteomic analysis of breast cancer cell membranes reveals unique proteins with potential roles in clinical cancer. Journal of Biological Chemistry, 278(8), 6482-6489. https://doi.org/10.1074/jbc.M210184200