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Differential expression of the multidrug resistance 1 (MDR1) protein in prostate cancer cells is independent from anticancer drug treatment and Y box binding protein 1 (YB-1) activity

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Abstract

Purpose

The development of a drug-resistant phenotype is the major challenge during treatment of castration-resistant prostate cancer (PC). In solid cancer entities, one of the major contributors to chemoresistance is the multidrug resistance 1 (MDR1) protein. Believed to be involved in the induction of MDR1 expression is the presence of anticancer drugs as well as the Y box binding protein 1 (YB-1).

Methods

Basal as well as drug-induced expression of MDR1 in established PC cell lines was assessed by Western blotting and mass spectrometry. Subsequently, the influence of YB-1 on MDR1 expression was examined via transient overexpression of YB-1.

Results

While LNCaP and PC-3 cells showed no detectable amounts of MDR1, the resistance factor was found to be expressed in 22Rv1 cells. Despite this difference, all three cell lines demonstrated similar growth behavior in the presence of the first-line chemotherapeutic agent docetaxel. Incubation of 22Rv1 cells with docetaxel, cabazitaxel, and abiraterone did not significantly alter MDR1 expression levels. Furthermore, overexpression of the MDR1 controlling factor YB-1 showed no impact on MDR1 expression levels.

Conclusions

MDR1 was detectable in the PC cell line 22Rv1. However, this study suggests that MDR1 is of less importance for drug resistance in PC cells than in other types of solid cancer. Furthermore, in contrast to YB-1 properties in other malignancies, MDR1 regulation through YB-1 seems to be unlikely.

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Abbreviations

PC:

Prostate cancer

MDR1:

Multidrug resistance 1

YB-1:

Y box binding protein 1

CYP17A1:

Cytochrome P450 17A1

GAPDH:

Glyceraldehyde 3-phosphate dehydrogenase

LC–MS/MS:

Liquid chromatography–tandem mass spectrometry

ABC:

ATP-binding cassette transporter

MRP1:

Multidrug resistance-associated protein 1

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Acknowledgments

The authors thank Anne Brandenburg and Katja Wittig for excellent technical assistance.

Conflict of interest

By way of disclosure of conflict of interest, the compound abiraterone acetate was kindly provided by Janssen-Cilag GmbH, Neuss, Germany, and the compound cabazitaxel was kindly provided by Sanofi-Aventis, Frankfurt/M., Germany.

Ethical standard

The manuscript does not contain clinical studies or patient data.

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Authors and Affiliations

  1. Department of Urology, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, 17475, Greifswald, Germany

    Madeleine Saupe, Lisa Rauschenberger, Melanie Preuß, Sebastian Fussek, Uwe Zimmermann, Martin Burchardt & Matthias B. Stope

  2. Department of Pharmacology, Center of Drug Absorption and Transport (C_DAT), University Medicine Greifswald, Felix-Hausdorf-Straße 3, 17487, Greifswald, Germany

    Stefan Oswald

  3. Department of Medical Biochemistry and Molecular Biology, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, 17475, Greifswald, Germany

    Reinhard Walther

  4. Institute for Laboratory and Transfusion Medicine, Heart and Diabetes Center North Rhine-Westphalia, Ruhr University Bochum, Georgstraße 11, 32545, Bad Oeynhausen, Germany

    Cornelius Knabbe

Authors
  1. Madeleine Saupe
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  2. Lisa Rauschenberger
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  3. Melanie Preuß
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  4. Stefan Oswald
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  5. Sebastian Fussek
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  8. Cornelius Knabbe
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  10. Matthias B. Stope
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Correspondence to Matthias B. Stope.

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Saupe, M., Rauschenberger, L., Preuß, M. et al. Differential expression of the multidrug resistance 1 (MDR1) protein in prostate cancer cells is independent from anticancer drug treatment and Y box binding protein 1 (YB-1) activity. World J Urol 33, 1481–1486 (2015). https://doi.org/10.1007/s00345-014-1469-0

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  • DOI: https://doi.org/10.1007/s00345-014-1469-0

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