在人类肺癌中，DNA拓扑异构酶I基因与CPT-11耐药性无关。
No alteration in DNA topoisomerase I gene related to CPT-11 resistance in human lung cancer.
作者信息
Ohashi N, Fujiwara Y, Yamaoka N, Katoh O, Satow Y, Yamakido M
机构信息
Second Department of Internal Medicine, Hiroshima University School of Medicine, Kasumi, Minami-ku.
出版信息
Jpn J Cancer Res. 1996 Dec;87(12):1280-7. doi: 10.1111/j.1349-7006.1996.tb03144.x.
Mutations and reduced expression of DNA topoisomerase I (topo I) gene have been shown to be important in the acquisition of resistance to camptothecin and its analogues in vitro, but their significance has not been verified in vivo. We investigated possible topo I gene mutations and topo I mRNA expression levels in 127 samples obtained from 56 patients with lung tumors, including patients who had developed clinical resistance to topo I inhibitors. No mutations were detected in any of the samples examined and expression levels did not differ significantly between clinically resistant cases and others. However, the topo I mRNA expression level was significantly higher in small cell lung carcinomas than in non-small cell lung carcinomas (P < 0.05). These results suggest that topo I mRNA levels may affect CPT-11 sensitivity in human lung cancer. However, topo I gene mutations and reduced topo I mRNA expression may not be the main mechanism of clinically acquired resistance to camptothecin analogues in vivo.
DNA拓扑异构酶I（拓扑异构酶I）基因的突变和表达降低已被证明在体外对喜树碱及其类似物的耐药性获得中起重要作用，但其在体内的意义尚未得到证实。我们调查了从56例肺癌患者中获得的127个样本中可能存在的拓扑异构酶I基因突变和拓扑异构酶I mRNA表达水平，其中包括对拓扑异构酶I抑制剂产生临床耐药性的患者。在所检测的任何样本中均未检测到突变，临床耐药病例与其他病例之间的表达水平无显著差异。然而，小细胞肺癌中的拓扑异构酶I mRNA表达水平显著高于非小细胞肺癌（P < 0.05）。这些结果表明，拓扑异构酶I mRNA水平可能影响人类肺癌对CPT - 11的敏感性。然而，拓扑异构酶I基因突变和拓扑异构酶I mRNA表达降低可能不是体内对喜树碱类似物临床获得性耐药的主要机制。
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