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

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)119-129
Number of pages11
JournalJournal of Neuro-Oncology
Volume84
Issue number2
DOIs
Publication statusPublished - 2007 Sep 1
Externally publishedYes

Fingerprint

Type II DNA Topoisomerase
Medulloblastoma
Etoposide
Neuroepithelial Neoplasms
Genes
Messenger RNA
Vincristine
Neuroepithelial Cells
Topoisomerase II Inhibitors
Neoplasms
Succinate Dehydrogenase
Astrocytoma
Glioblastoma
Reverse Transcription
Gene Expression
Polymerase Chain Reaction

Keywords

  • Chemotherapy
  • DNA topoisomerase II
  • Etoposide
  • Glioblastoma
  • Medulloblastoma

ASJC Scopus subject areas

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

Cite this

Enhanced expression of DNA topoisomerase II genes in human medulloblastoma and its possible association with etoposide sensitivity. / Uesaka, Toshio; Shono, Tadahisa; Kuga, Daisuke; Suzuki, Satoshi O.; Niiro, Hiroaki; Miyamoto, Kyoko; Matsumoto, Kenichi; Mizoguchi, Masahiro; Ohta, Masaru; Iwaki, Toru; Sasaki, Tomio.

In: Journal of Neuro-Oncology, Vol. 84, No. 2, 01.09.2007, p. 119-129.

Research output: Contribution to journalArticle

Uesaka, T, Shono, T, Kuga, D, Suzuki, SO, Niiro, H, Miyamoto, K, Matsumoto, K, Mizoguchi, M, Ohta, M, Iwaki, T & Sasaki, T 2007, 'Enhanced expression of DNA topoisomerase II genes in human medulloblastoma and its possible association with etoposide sensitivity', Journal of Neuro-Oncology, vol. 84, no. 2, pp. 119-129. https://doi.org/10.1007/s11060-007-9360-0
Uesaka, Toshio ; Shono, Tadahisa ; Kuga, Daisuke ; Suzuki, Satoshi O. ; Niiro, Hiroaki ; Miyamoto, Kyoko ; Matsumoto, Kenichi ; Mizoguchi, Masahiro ; Ohta, Masaru ; Iwaki, Toru ; Sasaki, Tomio. / Enhanced expression of DNA topoisomerase II genes in human medulloblastoma and its possible association with etoposide sensitivity. In: Journal of Neuro-Oncology. 2007 ; Vol. 84, No. 2. pp. 119-129.
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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.",
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