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Glypican-3 is involved in cellular protection against mitoxantrone in gastric carcinoma cells

Oncogene volume 23, pages 945–955 (2004)Cite this article

Abstract

Elevated expression of the heparan sulphate proteoglycan glypican-3 (GPC3) was found on mRNA and protein levels in the atypical multidrug-resistant gastric carcinoma cell line EPG85-257RNOV, which was established by in vitro selection against mitoxantrone. In order to elucidate a putative role of GPC3 in the drug-resistant phenotype, the mitoxantrone-resistant cell line EPG85-257RNOV was transfected with an expression vector construct carrying an anti-GPC3 hammerhead ribozyme. It could be demonstrated that in anti-GPC3 ribozyme-transfected cell clones, the GPC3-specific mRNA and corresponding protein expression levels were decreased to levels that are similar to those observed in nonresistant, parental cells. The anti-GPC3 ribozyme-containing clones reduced the mitoxantrone resistance level up to 21% of the original resistance and the crossresistance against etoposide to 33% of the original value. This reversal of drug resistance was accompanied by an increased cellular mitoxantrone accumulation in the anti-GPC3 ribozyme-expressing cells. In conclusion, it was verified that GPC3 is involved in the cellular protection against mitoxantrone in the atypical multidrug-resistant gastric carcinoma cell line EPG85-257RNOV.

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Acknowledgements

This work was supported by a grant from the Deutsche Krebshilfe (10-1313-La 3). We thank Yutaka Midorikawa, Hiroyuki Aburatani and Hiroko Iwanari for providing us with the anti-GPC3 mAb K6534.

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Authors and Affiliations

  1. Institute of Pathology, Charité, Campus Mitte, Humboldt University Berlin, Schumannstr. 20/21, Berlin, D-10117, Germany

    Anke Wichert, Alexandra Stege, Per Sonne Holm & Hermann Lage

  2. Genome Science Division, University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo, 153-8944, Japan

    Yutaka Midorikawa

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  1. Anke Wichert
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  2. Alexandra Stege
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  3. Yutaka Midorikawa
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Correspondence to Hermann Lage.

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Wichert, A., Stege, A., Midorikawa, Y. et al. Glypican-3 is involved in cellular protection against mitoxantrone in gastric carcinoma cells. Oncogene 23, 945–955 (2004). https://doi.org/10.1038/sj.onc.1207237

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