Determination of the Proteomic Response to Lapatinib Treatment using a comprehensive and reproducible ion-current-based proteomics strategy.

Journal of proteomics and genomics research Pub Date : 2013-01-01 Epub Date: 2013-09-08 DOI:10.14302/issn.2326-0793.jpgr-13-257

Kathleen O'Connell, Jun Li, Frank Engler, Kim Hennessy, Fiona O'Neill, Robert M Straubinger, Jun Qu, Robert O'Connor

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引用次数: 1

Abstract

Lapatinib, a small molecule tyrosine kinase inhibitor is currently used in the treatment of HER2-positive breast cancer. The aim of this study was to further understanding of lapatinib response for the development of novel treatment lapatinib-focussed treatment strategies. HER2-overexpressing SKBR3 breast cancer cells were treated with lapatinib for 12 hours and the resultant proteome analyzed by a comprehensive ion-current-based LC-MS strategy. Among the 1224 unique protein identified from SKBR3 cell lysates, 67 showed a significant change in protein abundance in response to lapatinib. Of these, CENPE a centromeric protein with increased abundance, was chosen for further validation. Knockdown and inhibition of CENPE demonstrated that CENPE enhances SKBR3 cell survival in the presence of lapatinib. Based on this study, CENPE inhibitors may warrant further investigation for use in combination with lapatinib.

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利用全面和可重复的基于离子电流的蛋白质组学策略测定拉帕替尼治疗的蛋白质组学反应。

拉帕替尼是一种小分子酪氨酸激酶抑制剂，目前用于治疗her2阳性乳腺癌。本研究的目的是进一步了解拉帕替尼的反应，以开发以拉帕替尼为重点的新型治疗策略。用拉帕替尼处理过表达her2的SKBR3乳腺癌细胞12小时，并通过基于离子电流的LC-MS综合策略分析产生的蛋白质组。在从SKBR3细胞裂解物中鉴定出的1224个独特蛋白中，67个蛋白丰度在拉帕替尼的作用下发生了显著变化。其中，选择了丰度增加的着丝粒蛋白CENPE进行进一步验证。对CENPE的敲除和抑制表明，在拉帕替尼的存在下，CENPE增强了SKBR3细胞的存活。基于这项研究，CENPE抑制剂与拉帕替尼联合使用可能需要进一步的研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Journal of proteomics and genomics research

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