title: Comparative proteomic analysis of cisplatin sensitive IGROV1 ovarian carcinoma cell line and its resistant counterpart IGROV1-R10.
abstract: Ovarian cancer is one of the leading causes of mortality due to gynaecological cancer. Despite a good response to surgery and initial chemotherapy essentially based on cisplatin (cis-diamino-dichloro-platinum(II) (CDDP)) compounds, late tumour detection and frequent recurrences with chemoresistance acquisition are responsible for poor prognosis. Several mechanisms have been implicated in CDDP resistance but they are not sufficient to exhaustively explain this resistance emergence. We applied a proteomic approach based on 2-DE coupled with MS to identify proteins associated with the chemoresistance process. We first established a proteomic pattern of the CDDP sensitive ovarian cell line IGROV1 using MALDI-TOF-MS and PMF. We then compared this 2-D pattern with that of the CDDP-resistant counterpart IGROV1-R10. Among the 40 proteins identified, cytokeratins 8 and 18 and aldehyde dehydrogenase 1 were overexpressed in IGROV1-R10, whereas annexin IV was down-regulated. These observations have been confirmed by Western blotting. The characterization of such variations could lead to the development of new protein markers or to the establishment of new therapeutic strategies. Moreover, the identification of proteins involved in CDDP resistance in ovarian tumours would be useful in completing our understanding on this complex mechanism.
authors.affiliation: Groupe Régional d'Etudes sur le Cancer, Caen, France. k.le.moguen@baclesse.fr
authors.forename: Karen
authors.initials: K
authors.lastname: Le Moguen
authors.forename: Hubert
authors.initials: H
authors.lastname: Lincet
authors.forename: Edwige
authors.initials: E
authors.lastname: Deslandes
authors.forename: Marie
authors.initials: M
authors.lastname: Hubert-Roux
authors.forename: Catherine
authors.initials: C
authors.lastname: Lange
authors.forename: Laurent
authors.initials: L
authors.lastname: Poulain
authors.forename: Pascal
authors.initials: P
authors.lastname: Gauduchon
authors.forename: Bruno
authors.initials: B
authors.lastname: Baudin
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D005260:Female; D006801:Humans; D009363:Neoplasm Proteins / Q000032:analysis; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D020543:Proteome / Q000187:drug effects / Q000378:metabolism; D040901:Proteomics
chemical_list: D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D020543:Proteome; D002945:Cisplatin