Luo Yuanming, Zhang Jindan, Liu Yanxin, Shaw Allan Christian, Wang Xiaorong, Wu Shuzhen, Zeng Xuan, Chen Jie, Gao Youhe, Zheng Dexian
National Laboratory of Medical Molecular Biology, Institute of Basic Med Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Mol Biotechnol. 2005 Mar;29(3):233-44. doi: 10.1385/MB:29:3:233.
Breast cancer is a leading cause of death for women. The underlying molecular mechanism is still not well understood. In this study, two-dimensional gel electrophoresis combined with mass spectrometry was used to analyze changes in the proteome of infiltrating ductal carcinoma compared to normal breast tissue. Ten sets of two-dimensional gels per experimental condition were analyzed and more than 500 spots each were detected. This revealed 39 spots for which expression in breast cancer cells were reproducibly altered more than twofold compared to normal controls (p < 0.01). These spots represented 25 different proteins after identification using the database search after mass spectrometry, comprising cell defense proteins, enzymes involved in glycolytic energy metabolism and homeostasis, protein folding and structural proteins, proteins involved in cytoskeleton and cell motility, and proteins involved in other functions. In addition, 28 nondifferentially expressed proteins with different functions were also mapped and identified, which might help to establish a two-dimensional gel electrophoresis reference map of human breast cancer. Our study shows that proteomics offers a powerful methodology to detect the proteins that show different expression patterns in breast cancer tissue and may provide an accurate molecular classification. The differentially expressed proteins may be used as potential candidate markers for diagnostic purposes or for determination of tumor sensitivity to therapy. The functional implications of the identified proteins are discussed.
乳腺癌是女性死亡的主要原因之一。其潜在的分子机制仍未完全明确。在本研究中，采用二维凝胶电泳结合质谱分析法，分析浸润性导管癌与正常乳腺组织相比蛋白质组的变化。对每个实验条件下的十组二维凝胶进行分析，每组检测到500多个斑点。结果显示，与正常对照相比，乳腺癌细胞中有39个斑点的表达反复变化超过两倍（p < 0.01）。质谱分析后通过数据库检索鉴定，这些斑点代表25种不同的蛋白质，包括细胞防御蛋白、参与糖酵解能量代谢和内稳态的酶、蛋白质折叠和结构蛋白、参与细胞骨架和细胞运动的蛋白质以及参与其他功能的蛋白质。此外，还对28种具有不同功能的非差异表达蛋白质进行了定位和鉴定，这可能有助于建立人类乳腺癌的二维凝胶电泳参考图谱。我们的研究表明，蛋白质组学提供了一种强大的方法来检测在乳腺癌组织中表现出不同表达模式的蛋白质，并可能提供准确的分子分类。差异表达的蛋白质可作为潜在的候选标志物用于诊断目的或确定肿瘤对治疗的敏感性。文中还讨论了已鉴定蛋白质的功能意义。
