Open AccessNo Alteration in DNA Topoisomerase I Gene Related to CPT‐11 Resistance in Human Lung Cancer
Author(s) -
Ohashi Nobuyuki,
Fujiwara Yasuhiro,
Yamaoka Naoki,
Katoh Osamu,
Satow Yukio,
Yamakido Michio
Publication year - 1996
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1996.tb03144.x
Subject(s) - topoisomerase , camptothecin , biology , gene expression , lung cancer , in vivo , gene , cancer research , messenger rna , microbiology and biotechnology , mutation , dna , genetics , pathology , medicine , biochemistry
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.