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

Authors: Uesaka, Toshio; Shono, Tadahisa1; Kuga, Daisuke; Suzuki, Satoshi; Niiro, Hiroaki; Miyamoto, Kyoko; Matsumoto, Kenichi; Mizoguchi, Masahiro; Ohta, Masaru; Iwaki, Toru; Sasaki, Tomio

Source: Journal of Neuro-Oncology, Volume 84, Number 2, September 2007 , pp. 119-129(11)

Publisher: Springer

Key:
Free Content - Free Content
New Content - New Content
Subscribed Content - Subscribed Content
Free Trial Content - Free Trial Content

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

Document Type: Research article

DOI: 10.1007/s11060-007-9360-0

Affiliations: 1: Email: tshono@ns.med.kyushu-u.ac.jp

The full text article is available for purchase

$42.00 plus tax

 

OR

Back to top

Key:
Free Content - Free Content
New Content - New Content
Subscribed Content - Subscribed Content
Free Trial Content - Free Trial Content
Page Help Click here for Page Help
Shopping cart
Tools
Sign in






Need to register?
Sign up here
Text size: A | A | A | A