Lack of a point mutation of human DNA topoisomerase II in multidrug-resistant anaplastic thyroid carcinoma cell lines.
DNA topoisomerases are major defined targets for a large variety of clinically important anticancer agents, including etoposide, adriamycin, and mitoxantrone. Mutations at amino acids 439, 450 and 803 of DNA topoisomerase II were examined in multiple anticancer drug-resistant anaplastic thyroid carcinomas (ten cell lines and three cancerous tissues) by reverse transcriptase-polymerase chain reaction (RT-PCR) and subsequent DNA sequencing. No mutation was found in these cell lines and tissues, but mdr1, mrp and/or lrp mRNA were expressed to a varying degree, and there was no significant difference in DNA topoisomerase IIalpha content among the cell lines and tissues as evaluated by Western blotting. Our experimental data indicate that overexpression of multidrug resistance-related mRNA is sufficient to confer drug resistance.
Satake
S
S
Department of Surgery, Teikyo University School of Medicine, Itabashi, Tokyo, Japan.
Sugawara
I
I
Watanabe
M
M
Takami
H
H
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000368:Aged; D001761:Bleomycin / Q000494:pharmacology; D015153:Blotting, Western; D002277:Carcinoma / Q000235:genetics*; D002945:Cisplatin / Q000494:pharmacology; D004250:DNA Topoisomerases, Type II / Q000235:genetics*; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005047:Etoposide / Q000494:pharmacology; D005260:Female; D019450:Genes, MDR / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000235:genetics*; D014407:Tumor Cells, Cultured; D020394:Vault Ribonucleoprotein Particles; D014750:Vincristine / Q000494:pharmacology; D000099187:Major Vault Protein
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D001761:Bleomycin; D002945:Cisplatin; D004250:DNA Topoisomerases, Type II; D004317:Doxorubicin; D005047:Etoposide; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D020394:Vault Ribonucleoprotein Particles; D014750:Vincristine; D000099187:Major Vault Protein