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Relationship of mRNA expressions of RanBP2 and topoisomerase II isoforms to cytotoxicity of amrubicin in human lung cancer cell lines

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Abstract

Purpose

RanBP2 is a small ubiquitin-like modifier ligase for DNA topoisomerase II (TopoII) and plays a role in maintaining chromosome stability by recruiting TopoII to centromeres during mitosis. Engineered-mice with low amounts of RanBP2 have been reported to form lung adenocarcinomas. Furthermore, in the murine embryonic fibroblasts, formation of chromatin bridges in anaphase, a distinctive feature of cells with impaired DNA decatenation by chemical inhibition of TopoII, has been reported. In this study, we tested whether the association between mRNA expression of the RanBP2 gene and chemosensitivity of a TopoII inhibitor, amrubicin could be seen.

Methods

Using a panel of 20 lung cancer cell lines, the mRNA expression levels of the RanBP2, TopoII-alpha and TopoII-beta genes were examined by quantitative real-time reverse transcription PCR. The in vitro cytotoxicity of amrubicin was assessed using a tetrazolium-based colorimetric assay (MTT assay).

Results

Although RanBP2 mRNA expression was infrequently downregulated in human lung cancer cell lines, significantly higher RanBP2 transcripts were observed in small cell lung cancer than non-small cell lung cancer. There were no correlations between chemosensitivity of amrubicin and mRNA expression levels of the RanBP2, TopoII-alpha and TopoII-beta genes.

Conclusions

Our in vitro results suggest that mRNA expressions of RanBP2 and TopoII isoforms are unlikely to be a predictive biomarker for the sensitivity to amrubicin.

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Acknowledgments

This work was supported in part by a Grant-in-Aid from the Japan Society for Promotion of Science, and a grant from the Aichi Cancer Research Foundation to Y. Horio.

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Authors and Affiliations

  1. Department of Thoracic Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan

    Yoshitsugu Horio, Junichi Shimizu, Shizu Ogawa & Toyoaki Hida

  2. Division of Molecular Oncology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan

    Hirotaka Osada & Yoshitaka Sekido

Authors
  1. Yoshitsugu Horio
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  2. Hirotaka Osada
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  3. Junichi Shimizu
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  4. Shizu Ogawa
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  5. Toyoaki Hida
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  6. Yoshitaka Sekido
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Correspondence to Yoshitsugu Horio.

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Horio, Y., Osada, H., Shimizu, J. et al. Relationship of mRNA expressions of RanBP2 and topoisomerase II isoforms to cytotoxicity of amrubicin in human lung cancer cell lines. Cancer Chemother Pharmacol 66, 237–243 (2010). https://doi.org/10.1007/s00280-009-1151-1

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  • DOI: https://doi.org/10.1007/s00280-009-1151-1

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