Comparative 2D-DIGE proteomic analysis of ovarian carcinoma cells: toward a reorientation of biosynthesis pathways associated with acquired platinum resistance |
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Authors: | Lincet Hubert Guével Blandine Pineau Charles Allouche Stéphane Lemoisson Edwige Poulain Laurent Gauduchon Pascal |
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Affiliation: | a Université de Caen Basse-Normandie, EA 1772, Unité “Biologie et Thérapies Innovantes des Cancers Localement Agressifs” IFR 146 ICORE, and Centre de Lutte Contre le Cancer François Baclesse, Avenue du général Harris, BP5026, F-14076 Caen Cedex 05, Franceb Proteomics Core Facility Biogenouest, Inserm, U625, Université de Rennes I, Campus de Beaulieu, Rennes, F-35042, Francec Université de Caen Basse-Normandie, Laboratoire de biologie moléculaire et cellulaire de la signalisation, UPRES EA 3919, IFR 146 ICORE, F-14032 Caen cedex, France |
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Abstract: | Ovarian cancer is the fifth most frequent cause of cancer death in women. Emergence of chemoresistance in the course of treatments with platinum drugs is in part responsible for therapeutic failures. In order to improve the understanding of the complex mechanisms involved in acquired platinum chemoresistance, we decided to compare the basal protein expression profile of the platinum-sensitive cell line OAW42 and that of its resistant counterpart OAW42-R by a proteomic approach. Reversed-phase HPLC pre-fractionated extracts from both cell lines were subjected to 2D-DIGE coupled to mass spectrometry (MS). Forty eight differentially expressed proteins were identified, 39 being up-regulated and 19 down-regulated in OAW42-R versus OAW42 cells. From the current knowledge on biological activities of most differentially expressed proteins, it can be inferred that the acquisition of resistance was associated with a global reorganization of biochemical pathways favoring the production of precursors for biosynthesis, and with the mobilization of macromolecule quality control mechanisms, preserving RNA and protein integrity under damage-inducing conditions. |
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Keywords: | 2D-DIGE Chemoresistance Ovarian cancer Cisplatin Metabolism Anabolic pathways |
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