Journal of Neuro-Oncology

, Volume 84, Issue 2, pp 119–129 | Cite as

Enhanced expression of DNA topoisomerase II genes in human medulloblastoma and its possible association with etoposide sensitivity

  • Toshio Uesaka
  • Tadahisa Shono
  • Daisuke Kuga
  • Satoshi O. Suzuki
  • Hiroaki Niiro
  • Kyoko Miyamoto
  • Kenichi Matsumoto
  • Masahiro Mizoguchi
  • Masaru Ohta
  • Toru Iwaki
  • Tomio Sasaki
Lab. Inverstigation-human/animal tissue

Abstract

Medulloblastoma (MB) is the most common malignant neuroepithelial tumor of childhood. The DNA topoisomerase II (Topo II) inhibitor etoposide has been widely used for the treatment of MBs; however, it remains unknown whether MB cells are more sensitive to etoposide than other malignant neuroepithelial tumor cells. In this study, we tested the chemosensitivities of malignant neuroepithelial tumors (26 glioblastomas, 9 anaplastic astrocytomas, and 5 MBs) to etoposide and vincristine using the succinate dehydrogenase inhibition test and found that MB cells are more sensitive to etoposide and more resistant to vincristine than other tumor cells. We performed quantitative reverse-transcription polymerase chain reaction to evaluate the expression of genes related to etoposide sensitivity, and found co-overexpression of DNA topoisomerase II (Topo II) α and β mRNA in MBs. In addition, the levels of Topo IIα and β mRNA in these tumors correlated with etoposide sensitivity. Immunohistochemical studies using surgical samples of these tumors demonstrated that the percentages of Topo IIα immunopositive cells (Topo IIα labeling index) correlated with those of Ki-67 immunopositive cells (MIB-1 labeling index); however, neither the Topo IIα nor the MIB-1 labeling index correlated with the levels of Topo IIα mRNA or etoposide sensitivity. Based on these observations, Topo IIα and β mRNA expression, but not the Topo IIα labeling index, might be a useful marker for sensitivity to etoposide in human malignant neuroepithelial tumors.

Keywords

Chemotherapy DNA topoisomerase II Etoposide Glioblastoma Medulloblastoma 

Notes

Acknowledgments

We thank Tomomi Yamada (Department of Medical Information Science, Kyushu University Hospital) for her invaluable assistance in statistical analysis, Saori Uchida for her excellent technical assistance, and Mikiko Hidaka and Emiko Uchiyama (Department of Neurosurgery, Kyushu University Graduate School of Medical Sciences) for assistance with manuscript preparation.

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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Toshio Uesaka
    • 1
  • Tadahisa Shono
    • 1
  • Daisuke Kuga
    • 1
  • Satoshi O. Suzuki
    • 2
  • Hiroaki Niiro
    • 3
  • Kyoko Miyamoto
    • 3
  • Kenichi Matsumoto
    • 1
  • Masahiro Mizoguchi
    • 1
  • Masaru Ohta
    • 4
  • Toru Iwaki
    • 2
  • Tomio Sasaki
    • 1
  1. 1.Department of Neurosurgery, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
  2. 2.Department of Neuropathology, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
  3. 3.Center for Cellular and Molecular MedicineKyushu University HospitalFukuokaJapan
  4. 4.Department of NeurosurgeryKyushu Rosai HospitalKitakyushuJapan

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