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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1998 Aug;89(8):855–861. doi: 10.1111/j.1349-7006.1998.tb00640.x

Differential Expression of DNA Topoisomerase IIα and IIβ Genes between Small Cell and Non‐small Cell Lung Cancer

Elisna Syahruddin 1, Tetsuya Oguri 1,✉, Toshiaki Takahashi 1, Takeshi Isobe 1, Yasuhiro Fujiwara 1,2, Michio Yamakido 1
PMCID: PMC5921913  PMID: 9765623

Abstract

DNA topoisomerase II (Topo II) inhibitors are widely used in lung cancer chemotherapy, but small cell lung cancer (SCLC) and non‐small cell lung cancer (NSCLC) show different sensitivity to them. In this study, we examined the gene expression levels of both isoforms of Topo II (IIα and IIβ) in lung cancer specimens to investigate the differential expression between SCLC and NSCLC. The expression levels of the Topo IIα and Topo IIβ genes were assessed in 80 autopsy samples (40 primary tumors and 40 corresponding normal lung tissues) by using the reverse transcription polymerase chain reaction. We found that the expression levels of the Topo IIα gene in tumors were significantly higher than those in normal lung tissues, and that those in SCLC were significantly higher than those in NSCLC. There were no significant differences in Topo IIβ gene expression between tumors and normal lung tissues and between SCLC and NSCLC. Furthermore, correlation analysis revealed that Topo IIα expression was correlated with Topo IIβ expression in both tumor and normal lung tissues. These results indicate that a difference exists in the regulation of the Topo II gene between lung tumors and normal lung tissues. Our finding of differential expression of Topo IIα between SCLC and NSCLC also suggests that the Topo IIα expression level is associated with sensitivity to Topo II inhibitors.

Keywords: key words, DNA topoisomerase IIα, DNA topoisomerase IIβ, Small cell lung cancer, Non‐small cell lung cancer, Drug resistance

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This study was supported by Grants‐in‐Aid from the Ministry of Education, Science and Culture and the Ministry of Health and Welfare of Japan, a Fellowship for Study at a Center of Excellence Abroad from the Japan Society for the Promotion of Science and grants from Osaka Cancer Research Foundation, and Chugai Seiyaku Co., Ltd. We are grateful to Drs. T. Tsuya, T. Ohune (Department of Respiratory Disease, Chugoku Rousai General Hospital) for providing autopsy samples. Thanks are also extended to Drs. O. Katoh (Department of Environment and Mutation, Research Institute for Radiation Biology and Medicine, Hiroshima University), and N. Ohashi (Department of Respiratory Disease, Hiroshima Red Cross Hospital and Atomic Bomb Survivors Hospital) for their practical suggestions during the study.

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