Kathleen O'Connell, Jun Li, Frank Engler, Kim Hennessy, Fiona O'Neill, Robert M Straubinger, Jun Qu, Robert O'Connor
{"title":"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。","authors":"Kathleen O'Connell, Jun Li, Frank Engler, Kim Hennessy, Fiona O'Neill, Robert M Straubinger, Jun Qu, Robert O'Connor","doi":"10.14302/issn.2326-0793.jpgr-13-257","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":90235,"journal":{"name":"Journal of proteomics and genomics research","volume":"1 3","pages":"27-42"},"PeriodicalIF":0.0000,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5642974/pdf/nihms908409.pdf","citationCount":"1","resultStr":"{\"title\":\"Determination of the Proteomic Response to Lapatinib Treatment using a comprehensive and reproducible ion-current-based proteomics strategy.\",\"authors\":\"Kathleen O'Connell, Jun Li, Frank Engler, Kim Hennessy, Fiona O'Neill, Robert M Straubinger, Jun Qu, Robert O'Connor\",\"doi\":\"10.14302/issn.2326-0793.jpgr-13-257\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":90235,\"journal\":{\"name\":\"Journal of proteomics and genomics research\",\"volume\":\"1 3\",\"pages\":\"27-42\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2013-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5642974/pdf/nihms908409.pdf\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of proteomics and genomics research\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.14302/issn.2326-0793.jpgr-13-257\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2013/9/8 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of proteomics and genomics research","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.14302/issn.2326-0793.jpgr-13-257","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2013/9/8 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
Determination of the Proteomic Response to Lapatinib Treatment using a comprehensive and reproducible ion-current-based proteomics strategy.
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.