Comprehensive proteomic analysis of breast cancer cell membranes reveals unique proteins with potential roles in clinical cancer
Comprehensive proteomic analysis of breast cancer cell membranes reveals unique proteins with potential roles in clinical cancer
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DOI：
10.1074/jbc.m210184200
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发表时间：
2003-02-21
影响因子：
4.8
通讯作者：
Terrett, JA
中科院分区：
文献类型：
--
作者：
Adam, PJ;Boyd, R;Terrett, JA
与癌细胞质膜相关的蛋白质富含已知的药物和抗体靶标以及已知在致癌所需的异常信号转导过程中起关键作用的其他蛋白质。我们在这里描述了一个蛋白质组学的过程，全面注释乳腺肿瘤细胞膜的蛋白质含量，并定义这些蛋白质的临床相关性。肿瘤来源的细胞系用于确保癌细胞特异性质膜蛋白的富集，因为难以纯化癌细胞，然后从临床材料获得良好的膜制剂。使用具有不同分子病理学的多个细胞系来代表乳腺癌的临床异质性。肽串联质谱检索了一个综合数据库，其中包含来自许多公共数据库（包括人类基因组序列草案）的已知和概念性蛋白质。这种质膜富集蛋白质组分析创建了500多种乳腺癌细胞系蛋白质的数据库，其中27%的蛋白质功能未知。我们的方法的价值是通过进一步详细分析的三个以前未表征的蛋白质，其临床相关性已被定义其独特的癌症表达谱和蛋白质结合伴侣，阐明在癌症中的潜在功能的鉴定。
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.