Microbead arrays for the analysis of ErbB receptor tyrosine kinase activation and dimerization in breast cancer cells.
Microbead arrays for the analysis of ErbB receptor tyrosine kinase activation and dimerization in breast cancer cells.
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用于分析乳腺癌细胞中 ErbB 受体酪氨酸激酶激活和二聚化的微珠阵列。
DOI：
10.1089/adt.2009.0208
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发表时间：
2010
影响因子：
1.8
通讯作者：
Luciw,PaulA
中科院分区：
文献类型：
--
作者：
Khan,ImranH;Zhao,Jing;Ghosh,Paramita;Ziman,Melanie;Sweeney,Colleen;Kung,Hsing-Jien;Luciw,PaulA
ErbB家族中的受体酪氨酸激酶（RTK）（EGFR、ErbB 2、ErbB 3和ErbB 4）与多种人类恶性肿瘤有关。因此，确定ErbB蛋白的表达和活化（二聚化/异源二聚化和磷酸化）对于确定其在癌症中的功能作用至关重要。研究ErbB家族RTKs分子功能的有效和全面的方法不仅需要改进诊断方法，而且还需要早期筛选靶向药物（如小分子抑制剂和治疗性抗体）。我们报告了3种多重微珠免疫测定法的发展，用于同时检测这些RTK的表达、蛋白质-蛋白质相互作用和磷酸化。这些新的多重免疫测定用于在2种乳腺癌细胞系（MDA-MB-453和MDA-MB-468）和表皮样癌细胞系（A431）中研究不同细胞活化条件下的ErbB RTK。结果通过免疫沉淀/蛋白质印迹证实。重要的是，多重免疫测定促进了EGF和神经调节蛋白激活细胞后这些细胞系的时程研究，揭示了ErbB家族RTK磷酸化的动力学。本研究证明了Luminex®多重系统作为研究这些RTK分子作用的不同方面的有效和综合方法的实用性。重要的是，该研究为多重微珠免疫测定方法的实用性提供了概念验证，该方法可能用于有效，稳健和快速筛选药物，特别是那些靶向这些有效信号分子的功能方面的药物。此外，本文所述的测定可用于癌症诊断和监测靶向RTK的ErbB家族的疗法的功效。
Receptor tyrosine kinases (RTKs) in the ErbB family (EGFR, ErbB2, ErbB3, and ErbB4) are implicated in a variety of human malignancies. Accordingly, determination of both expression and activation (dimerization/heterodimerization and phosphorylation) of ErbB proteins is critical in defining their functional role in cancer. Efficient and comprehensive methods to study molecular functions of ErbB family of RTKs are needed not only for improvements in diagnostics but also for early screening of targeted drugs (eg, small molecule inhibitors and therapeutic antibodies). We report development of 3 multiplex microbead immunoassays for simultaneous detection of expression, protein–protein interactions, and phosphorylation of these RTKs. These novel multiplex immunoassays were used to study ErbB RTKs under different cell activation conditions in 2 breast cancer cell lines (MDA-MB-453 and MDA-MB-468) and an epidermoid cancer cell line (A431). The results were confirmed by immunoprecipitation/western blot. Importantly, the multiplex immunoassay facilitated time-course studies in these cell lines after cell activation with EGF and neuregulin, revealing the kinetics of phosphorylation of the ErbB family RTKs. This study demonstrates the utility of the Luminex® multiplex system as an efficient and comprehensive approach to study different aspects of molecular roles of these RTKs. Importantly, the study provides proof-of-concept for the utility of the multiplex microbead immunoassay approach for potential use in efficient, robust, and rapid screening of drugs, particularly those targeting functional aspects of these potent signaling molecules. In addition, the assays described here may be useful for cancer diagnostics and monitoring efficacy of therapy targeting the ErbB family of RTKs.
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ErbB-2/ErbB-3 异二聚体的选择性形成取决于表皮生长因子样配体的 ErbB-3 亲和力*
影响因子：
4.8
作者：
C. Stortelers;S. P. van der Woning;Saskia Jacobs;M. Wingens;E. J. V. van Zoelen
通讯作者：
E. J. V. van Zoelen
基于免疫蛋白质组学的多重微珠悬浮阵列的生物标志物检测和分子分析
DOI：
10.1002/9781119977438.ch11
发表时间：
2011
期刊：
J. Comput. Syst. Sci.
影响因子：
--
作者：
V. V. Krishhan;I. Khan;P. Luciw
通讯作者：
P. Luciw
DOI：
10.1073/pnas.89.6.2287
发表时间：
1992-03-15
影响因子：
11.1
作者：
LUPU, R;COLOMER, R;LIPPMAN, ME
通讯作者：
LIPPMAN, ME
影响因子：
7.4
作者：
T. Veenstra;DaRue Prieto;T. Conrads
通讯作者：
T. Veenstra;DaRue Prieto;T. Conrads
DOI：
--
发表时间：
2003-04
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
J. Anido;P. Matar;J. Albanell;M. Guzman;F. Rojo;J. Arribas;S. Averbuch;J. Baselga
通讯作者：
J. Anido;P. Matar;J. Albanell;M. Guzman;F. Rojo;J. Arribas;S. Averbuch;J. Baselga