| Comparative proteomic analysis of paclitaxel sensitive A2780 epithelial ovarian cancer and its resistant counterpart A2780TC1 by 2D-DIGE: the role of ERp57. | |
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MedLine Citation:
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PMID: 19199837 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Epithelial ovarian cancer is the leading cause of gynaecological cancer mortality. Despite good response to surgery and initial chemotherapy, chemoresistance occurrence represents a major obstacle to a successful therapy. To better understand biological mechanisms at the basis of paclitaxel resistance, a comparative proteomic approach based on DIGE coupled with mass spectrometry (MALDI-TOF and LC-MS/MS) was applied to the human epithelial ovarian cancer cell lines A2780 and its paclitaxel resistant counterpart A2780TC1. Most of the differentially expressed proteins between the two cell lines belong to the class of stress response (29%), metabolism (21%) and cell cycle and apoptosis (17%). We focused on proteins which were most strongly modulated by paclitaxel resistance and in particular on the disulphide isomerase ERp57, which may represent a chemoresistance biomarker. ERp57 was found to interact with class III ss-tubulin (TUBB3), involved in paclitaxel resistance in ovarian and other cancers. Moreover we demonstrated a novel localization of this protein in cytoskeleton and described that ERp57/TUBB3 interaction occurs also in the nuclear compartment and in association with a multimeric complex formed by nucleolin, nucleophosmin, hnRNPK and mortalin. Our data suggest that ERp57 plays an important role in chemoresistance mechanisms in ovarian cancer by modulating the attachment of microtubules to chromosomes and participating to the dynamic reorganization of the mitotic spindle after paclitaxel treatment through its interaction with TUBB3. |
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Authors:
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Lucia Cicchillitti; Michela Di Michele; Andrea Urbani; Cristiano Ferlini; Maria Benedetta Donati; Giovanni Scambia; Domenico Rotilio |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2009-2-9 |
Journal Detail:
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Title: Journal of proteome research Volume: - ISSN: 1535-3907 ISO Abbreviation: J. Proteome Res. Publication Date: 2009 Feb |
Date Detail:
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Created Date: 2009-2-9 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101128775 Medline TA: J Proteome Res Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
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