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Differential expression of DNA topoisomerase II alpha and II beta genes between small cell and non-small cell lung
E Syahruddin1, T Oguri, T Takahashi
1Second Department of Internal Medicine, Hiroshima University School of Medicine.
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 (II alpha and II beta) in lung cancer specimens to investigate the differential expression between SCLC and NSCLC. The expression levels of the Topo II alpha and Topo II beta 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 II alpha 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 II beta gene expression between tumors and normal lung tissues and between SCLC and NSCLC. Further-more, correlation analysis revealed that Topo II alpha expression was correlated with Topo II beta 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 II alpha between SCLC and NSCLC also suggests that the Topo II alpha expression level is associated with sensitivity to Topo II inhibitors.
Insights
Lung cancer drug sensitivity differs between small cell (SCLC) and non-small cell (NSCLC) types. DNA topoisomerase II alpha (Topo II alpha) gene expression is higher in tumors, especially SCLC, suggesting it impacts treatment response.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- DNA topoisomerase II (Topo II) inhibitors are crucial in lung cancer chemotherapy.
- Differential sensitivity to Topo II inhibitors exists between small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC).
- Understanding Topo II isoform expression may elucidate these sensitivity differences.
Purpose of the Study:
- To investigate differential gene expression of DNA topoisomerase II alpha (Topo II alpha) and Topo II beta isoforms in lung cancer.
- To compare Topo II isoform expression between SCLC and NSCLC.
- To explore the association between Topo II expression and sensitivity to Topo II inhibitors.
Main Methods:
- Gene expression levels of Topo II alpha and Topo II beta were assessed.
- Samples included 40 primary lung tumors and 40 corresponding normal lung tissues from autopsy.
- Reverse transcription polymerase chain reaction (RT-PCR) was employed for gene expression analysis.
Main Results:
- Topo II alpha expression was significantly elevated in lung tumors compared to normal tissues.
- Topo II alpha expression was significantly higher in SCLC tumors than in NSCLC tumors.
- No significant differences in Topo II beta expression were observed between tumor and normal tissues, or between SCLC and NSCLC.
Conclusions:
- Differential regulation of Topo II alpha exists between lung tumors and normal lung tissues.
- The elevated Topo II alpha expression in SCLC compared to NSCLC suggests a role in differential drug sensitivity.
- Topo II alpha expression levels are potentially associated with patient response to Topo II inhibitor chemotherapy.
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