Comparison of Normal and Breast Cancer Cell Lines Using Proteome, Genome, and Interactome Data

Normal and cancer cell line proteomes were profiled using high throughput mass spectrometry
techniques. Application of protein-level and peptide-level sample fractionation combined with LC−MS/MS analysis enabled identification of 2235 unmodified proteins representing a broad range of
functional and compartmental classes. An iterative multistep search strategy was used to identify post-translational modifications, revealing several proteins that are preferentially modified in cancer cells.
Information regarding both unmodified and modified protein forms was combined with publicly
available gene expression and protein−protein interaction data. The resulting integrated dataset revealed
several functionally related proteins that are differentially regulated between normal and cancer cell
lines.
Keywords: post-translational modifications • breast cancer • proteome • mass spectrometry • membrane proteins
• high throughput • subcellular • multidimensional liquid chromatography • functional genomics • pathways

本研究采用高通量质谱技术对正常细胞系与癌细胞系的蛋白质组（proteome）进行了表征分析。通过蛋白质水平与肽段水平的样品分级分离结合液相色谱-串联质谱（LC−MS/MS）分析，成功鉴定出2235种未修饰蛋白质，这些蛋白质涵盖了广泛的功能类别与亚细胞分区类别。本研究采用迭代多步检索策略鉴定翻译后修饰（post-translational modifications），发现了若干在癌细胞中存在优先修饰现象的蛋白质。将未修饰与修饰蛋白质形式的相关信息，与公开获取的基因表达及蛋白质-蛋白质相互作用数据进行整合。最终得到的整合数据集揭示了多组在正常细胞系与癌细胞系间存在差异调控的功能相关蛋白质。
关键词：翻译后修饰 • 乳腺癌 • 蛋白质组 • 质谱 • 膜蛋白 • 高通量 • 亚细胞 • 多维液相色谱 • 功能基因组学 • 通路