The analysis of doxorubicin resistance in human breast cancer cells using antibody microarrays
The analysis of doxorubicin resistance in human breast cancer cells using antibody microarrays
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DOI：
10.1158/1535-7163.mct-06-0190
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发表时间：
2006-08-01
影响因子：
5.7
通讯作者：
Cawkwell, Lynn
中科院分区：
文献类型：
--
作者：
Smith, Laura;Watson, Mark B.;Cawkwell, Lynn
阿霉素被认为是治疗乳腺癌患者最有效的药物。不幸的是，对该药物的耐药性很常见，这是成功治疗的主要障碍。能够预测治疗反应的新型生物标志物的鉴定可能允许针对个体患者定制治疗。抗体微阵列提供了一种强大的新技术，可以同时对许多蛋白质进行全局比较分析。该技术可以识别一组蛋白质来区分耐药样品和药物敏感样品。 Panorama 细胞信号抗体微阵列用于分析 MDA-MB-231 乳腺癌细胞系和一种新型衍生物，该衍生物在临床相关浓度下对阿霉素表现出显着的耐药性。该微阵列包含选自多种途径的 224 种抗体，包括细胞凋亡和细胞信号传导途径。使用标准 >= 2.0 倍截止值来确定差异表达的蛋白质。丝裂原激活蛋白激酶激活单磷酸酪氨酸（磷酸化细胞外信号调节激酶；减少 2.8 倍）、细胞周期蛋白 D2（减少 2.5 倍）、细胞角蛋白 18（减少 2.5 倍）、细胞周期蛋白 B1（减少 2.4 倍）和异质核核糖核蛋白 m3-m4（减少 2.0 倍）的表达减少与阿霉素耐药性。利用蛋白质印迹来确认抗体微阵列实验的结果。这些结果表明抗体微阵列可用于识别新型生物标志物，进一步验证可能揭示化疗耐药机制并识别潜在的治疗靶点。
Doxorubicin is considered to be the most effective agent in the treatment of breast cancer patients. Unfortunately, resistance to this agent is common, representing a major obstacle to successful treatment. The identification of novel biomarkers that are able to predict treatment response may allow therapy to be tailored to individual patients. Antibody microarrays provide a powerful new technique, enabling the global comparative analysis of many proteins simultaneously. This technology may identify a panel of proteins to discriminate between drug-resistant and drug-sensitive samples. The Panorama Cell Signaling Antibody Microarray was exploited to analyze the MDA-MB-231 breast cancer cell line and a novel derivative, which displays significant resistance to doxorubicin at clinically relevant concentrations. The microarray comprised 224 antibodies selected from a variety of pathways, including apoptotic and cell signaling pathways. A standard >= 2.0-fold cutoff value was used to determine differentially expressed proteins. A decrease in the expression of mitogen-activated protein kinase-activated monophosphotyrosine (phosphorylated extracellular signal-regulated kinase; 2.8-fold decrease), cyclin D2 (2.5-fold decrease), cytokeratin 18 (2.5-fold decrease), cyclin B1 (2.4-fold decrease), and heterogeneous nuclear ribonucleoprotein m3-m4 (2.0-fold decrease) was associated with doxorubicin resistance. Western blotting was exploited to confirm results from the antibody microarray experiment. These results suggest that antibody microarrays can be used to identify novel biomarkers and further validation may reveal mechanisms of chemotherapy resistance and identify potential therapeutic targets.