Differential expression of DNA topoisomerase I gene between CPT-11 acquired- and native-resistant human pancreatic tumor cell lines: detected by RNA/PCR-based quantitation assay.
RNA/PCR quantitation method was developed to determine DNA Topoisomerase I(Topo I)-specific mRNA in order to study its gene expression in CPT-11 sensitive, acquired- or native-resistant human pancreatic tumor cell lines. The results were supported by Northern blotting and Western blotting analyses. Acquired-resistant cells have shown decreased levels of Topo I mRNA, compared with their parental cells. On the contrary, in the wild type cells no correlation was shown between sensitivity and gene expression. On the other, specific Topo I activity of the native resistant cell lines was fairly lower than that of sensitive cell lines, suggesting that immunoreactive Topo I protein contains low levels of active form enzyme which could be targets of CPT-11 in these native-resistant ones. Finally, the different mechanisms might be operative between acquired- and native-resistant tumor cells.
Takeda
S
S
Division of Chemotherapy, National Kyushu Cancer Center, Fukuoka, Japan.
Shimazoe
T
T
Sato
K
K
Sugimoto
Y
Y
Tsuruo
T
T
Kono
A
A
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001483:Base Sequence; D015152:Blotting, Northern; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004264:DNA Topoisomerases, Type I / Q000235:genetics* / Q000378:metabolism; D004351:Drug Resistance / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000077146:Irinotecan; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010190:Pancreatic Neoplasms; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D000077146:Irinotecan; D004264:DNA Topoisomerases, Type I; D002166:Camptothecin