Relationship between topoisomerase II levels and resistance to topoisomerase II inhibitors in lung cancer cell lines.
Topoisomerase II is a key target of many anticancer drugs used to treat lung cancer. We measured the expression of topoisomerase II alpha and beta mRNA's and also the levels of cellular topoisomerase II alpha and beta protein and concluded that topoisomerase II alpha levels are important in cellular resistance to the topoisomerase II inhibitors examined. This can be clearly seen in pairs of matched cell lines. However, when looking at a panel of cell lines with a range of histological types the importance of the enzyme can be masked by other cellular characteristics such as repair and detoxification mechanisms.
Houlbrook
S
S
Molecular Oncology Laboratories, Imperial Cancer Research Fund, John Radcliffe Hospital, Oxford, U.K.
Harris
A L
AL
Carmichael
J
J
Stratford
I J
IJ
D000677:Amsacrine / Q000633:toxicity; D000970:Antineoplastic Agents / Q000633:toxicity*; D015153:Blotting, Western; D002460:Cell Line; D002699:Chlorambucil / Q000633:toxicity; D004250:DNA Topoisomerases, Type II / Q000009:adverse effects* / Q000096:biosynthesis*; D004317:Doxorubicin / Q000633:toxicity; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000633:toxicity*; D005047:Etoposide / Q000633:toxicity; D006801:Humans; D008175:Lung Neoplasms; D008942:Mitoxantrone / Q000633:toxicity; D012333:RNA, Messenger / Q000096:biosynthesis; D014158:Transcription, Genetic / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D000677:Amsacrine; D002699:Chlorambucil; D005047:Etoposide; D004317:Doxorubicin; D008942:Mitoxantrone; D004250:DNA Topoisomerases, Type II