EXPRESSION OF TOPOISOMERASE-II-ALPHA AND TOPOISOMERASE-II-BETA IN AN ADENOCARCINOMA CELL-LINE CARRYING AMPLIFIED TOPOISOMERASE-II-ALPHA AND RETINOIC ACID RECEPTOR-ALPHA GENES

被引:25
作者
COUTTS, J [1 ]
PLUMB, JA [1 ]
BROWN, R [1 ]
KEITH, WN [1 ]
机构
[1] BEATSON LABS,CRC,DEPT MED ONCOL,ALEXANDER STONE BLDG,GARSCUBE ESTATE,GLASGOW G61 1BD,SCOTLAND
关键词
D O I
10.1038/bjc.1993.430
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Human topoisomerase II enzymes are targets for a number of widely used anticancer agents. We have analysed a lung adenocarcinoma cell line CALU3, which has co-amplified topoisomerase IIalpha and ERBB2 sequences, for the structure of the amplicon and for expression of both topoisomerase IIalpha and beta. The region of chromosome 17q amplified in CALU3 also includes the retinoic acid receptor alpha locus and is therefore similar to the amplicon observed in breast cancers carrying amplified topoisomerase IIalpha and retinoic acid receptor sequences. The use of fluorescence in situ hybridisation localises the amplified topoisomerase IIalpha sequences to a cluster on one chromosome with single copies localised to others. CALU3 expresses high levels of topoisomerase IIalpha as determined by Western blot, immunofluorescence and enzyme activity. The enzyme activity extracted from CALU3 is sensitive to inhibition by the topoisomerase II poison etoposide. Topoisomerase IIbeta expression was observed in three lung cancer cell lines including CALU3 and was confined to the nucleoli. Thus, the CALU3 cell line is an ideal model to study the amplification and expression of topoisomerase IIalpha in adenocarcinomas.
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页码:793 / 800
页数:8
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