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Nuclear metallothionein expression correlates with cisplatin resistance of ovarian cancer cells and poor clinical outcome

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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.

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Authors and Affiliations

  1. Institute of Pathology, Charité Campus Mitte, Charitéplatz 1, 10117, Berlin, Germany

    Paweł Surowiak, Verena Materna, Manfred Dietel & Hermann Lage

  2. Department of Histology and Embryology, University School of Medicine, ul. Chałubińskiego 6a, 50-356, Wrocław, Poland

    Paweł Surowiak & Maciej Zabel

  3. Lower Silesian Centre of Oncology, pl. Hirszfelda 12, 53-413, Wrocław, Poland

    Paweł Surowiak, Adam Maciejczyk & Marek Pudełko

  4. Department of Obstetrics and Gynaecology, University School of Medicine, ul. Polna 33, 60-535, Poznań, Poland

    Ewa Markwitz & Marek Spaczyński

  5. Department of Histology and Embryology, University School of Medicine, ul. Święcickiego 6, 60-781, Poznań, Poland

    Maciej Zabel

Authors
  1. Paweł Surowiak
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  2. Verena Materna
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  3. Adam Maciejczyk
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  4. Marek Pudełko
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  5. Ewa Markwitz
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  6. Marek Spaczyński
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  7. Manfred Dietel
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  8. Maciej Zabel
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  9. Hermann Lage
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Correspondence to Hermann Lage.

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Surowiak, P., Materna, V., Maciejczyk, A. et al. Nuclear metallothionein expression correlates with cisplatin resistance of ovarian cancer cells and poor clinical outcome. Virchows Arch 450, 279–285 (2007). https://doi.org/10.1007/s00428-006-0362-7

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  • DOI: https://doi.org/10.1007/s00428-006-0362-7

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