title: Nuclear metallothionein expression correlates with cisplatin resistance of ovarian cancer cells and poor clinical outcome.
abstract: Elevated metallothionein (MT) expression in ovarian cancers treated with cisplatin-based schemes represents an unfavorable prognostic index. MT expression is significantly higher in tumor samples obtained after chemotherapy. The present study aimed at examining MT expression in ovarian carcinoma cells sensitive (A2780) or resistant (A2780RCIS) against platinum drug treatment as well as examining effects of exposure to cisplatin on MT expression. Subcellular expression of MT was evaluated also in samples originating from 73 ovarian tumors. Cisplatin-resistant A2780RCIS cells were exposed to increasing cisplatin concentrations, and the subcellular expression of MT was determined by immunocytochemistry. The studies demonstrated that cisplatin-resistant A2780RCIS cells exposed to cisplatin typically manifested a nuclear MT expression. The study demonstrated also that exposure to cisplatin was paralleled by growing MT expression in cell nuclei. The nuclear expression of MT was also found to be specific for ovarian cancers of poor clinical outcome. No relationship could be demonstrated between cytoplasmic expression of MT and clinical variables. Nuclear MT expression is induced by cisplatin and seems to protect DNA in the cells from toxic effects of the drug.
authors.affiliation: Institute of Pathology, Charité Campus Mitte, Charitéplatz 1, 10117, Berlin, Germany.
authors.forename: Paweł
authors.initials: P
authors.lastname: Surowiak
authors.forename: Verena
authors.initials: V
authors.lastname: Materna
authors.forename: Adam
authors.initials: A
authors.lastname: Maciejczyk
authors.forename: Marek
authors.initials: M
authors.lastname: Pudełko
authors.forename: Ewa
authors.initials: E
authors.lastname: Markwitz
authors.forename: Marek
authors.initials: M
authors.lastname: Spaczyński
authors.forename: Manfred
authors.initials: M
authors.lastname: Dietel
authors.forename: Maciej
authors.initials: M
authors.lastname: Zabel
authors.forename: Hermann
authors.initials: H
authors.lastname: Lage
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D008668:Metallothionein / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D008668:Metallothionein; D002945:Cisplatin