Syahruddin E, Oguri T, Takahashi T, Isobe T, Fujiwara Y, Yamakido M
Second Department of Internal Medicine, Hiroshima University School of Medicine.
Jpn J Cancer Res. 1998 Aug;89(8):855-61. doi: 10.1111/j.1349-7006.1998.tb00640.x.
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.
DNA拓扑异构酶II(Topo II)抑制剂广泛应用于肺癌化疗,但小细胞肺癌(SCLC)和非小细胞肺癌(NSCLC)对其表现出不同的敏感性。在本研究中,我们检测了肺癌标本中Topo II两种同工型(IIα和IIβ)的基因表达水平,以研究SCLC和NSCLC之间的差异表达。通过逆转录聚合酶链反应评估了80份尸检样本(40份原发性肿瘤和40份相应的正常肺组织)中Topo IIα和Topo IIβ基因的表达水平。我们发现肿瘤中Topo IIα基因的表达水平显著高于正常肺组织,且SCLC中的表达水平显著高于NSCLC。肿瘤与正常肺组织之间以及SCLC与NSCLC之间Topo IIβ基因表达无显著差异。此外,相关性分析显示,肿瘤和正常肺组织中Topo IIα表达均与Topo IIβ表达相关。这些结果表明,肺肿瘤与正常肺组织之间Topo II基因的调控存在差异。我们发现SCLC和NSCLC之间Topo IIα表达存在差异,这也表明Topo IIα表达水平与对Topo II抑制剂的敏感性相关。