Elevated expression of DNA topoisomerase II in camptothecin-resistant human tumor cell lines.
In a previous study, we established camptothecin (CPT)-resistant cell lines, A549/CPT and HT-29/CPT, from human lung cancer A549 and human colon cancer HT-29. A549/CPT was shown to express similar amounts of DNA topoisomerase I (topo I) as the parental line, and HT-29/CPT was shown to express lower amounts of topo I than its parental line. DNA topoisomerases I and II are known to be functionally related. In the present study, the possible alterations in topo II expression were examined in these human CPT-resistant lines. In A549/CPT and HT-29/CPT, the cellular contents of topo II and its mRNA were elevated over that seen in each parental line. Nuclear extracts from A549/CPT and HT-29/CPT showed higher topo II activity than those from the corresponding parental lines when the same amounts of nuclear protein were used. Topo II was partially purified from HT-29 and HT-29/CPT by hydroxylapatite column chromatography, and the enzyme activities were compared. HT-29/CPT showed higher topo II activity in the hydroxylapatite column-eluted fractions than HT-29. These results indicate the possible activation of topo II expression in the CPT-resistant cell lines.
Sugimoto
Y
Y
Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo.
Tsukahara
S
S
Oh-hara
T
T
Liu
L F
LF
Tsuruo
T
T
D000970:Antineoplastic Agents / Q000494:pharmacology; D002166:Camptothecin / Q000494:pharmacology*; D002460:Cell Line; D002467:Cell Nucleus / Q000201:enzymology; D003110:Colonic Neoplasms; D004250:DNA Topoisomerases, Type II / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D004351:Drug Resistance; D006801:Humans; D007700:Kinetics; D008175:Lung Neoplasms; D008970:Molecular Weight; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification
D000970:Antineoplastic Agents; D012333:RNA, Messenger; D004250:DNA Topoisomerases, Type II; D002166:Camptothecin