Relationship between expression of topoisomerase II isoforms and intrinsic sensitivity to topoisomerase II inhibitors in breast cancer cell lines.
Relationship between expression of topoisomerase II isoforms and intrinsic sensitivity to topoisomerase II inhibitors in breast cancer cell lines.
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DOI：
10.1038/bjc.1995.529
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发表时间：
1995-12
影响因子：
8.8
通讯作者：
Hickson ID
中科院分区：
文献类型：
--
作者：
Houlbrook S;Addison CM;Davies SL;Carmichael J;Stratford IJ;Harris AL;Hickson ID
拓扑异构酶 II 是许多用于治疗乳腺癌的抗癌药物的关键靶点。在人类细胞中，有两种密切相关但表达差异的拓扑异构酶 II 亚型，分别称为拓扑异构酶 II α 和 β。在这里，我们报告了针对拓扑异构酶 II 180 kDa 形式（β 亚型）C 端结构域片段的新多克隆抗体的产生，该抗体不会与 170 kDa 形式（α 亚型）发生交叉反应。使用该抗体以及对拓扑异构酶 II 170 kDa 亚型特异的多克隆抗体，我们检查了一组人乳腺癌细胞系对不同类别拓扑异构酶 II 抑制剂的敏感性与拓扑异构酶 II α 和 β 蛋白的细胞水平之间的关系。我们发现对安吖啶的敏感性与拓扑异构酶 II α 蛋白的表达水平相关，对依托泊苷的敏感性与拓扑异构酶 II β 蛋白的表达水平具有类似的相关性。这些细胞系对米托蒽醌的敏感性与拓扑异构酶 II 两种亚型的细胞水平之间也存在相关性。拓扑异构酶 II α 或 β mRNA 水平与乳腺癌细胞系对拓扑异构酶 II 抑制剂的敏感性或拓扑异构酶 II 蛋白表达水平之间没有发现任何关系。
Topoisomerase II is a key target for many anti-cancer drugs used to treat breast cancer. In human cells there are two closely related, but differentially expressed, topoisomerase II isoforms, designated topoisomerase II alpha and beta. Here, we report the production of a new polyclonal antibody raised against a fragment of the C-terminal domain of the 180 kDa form of topoisomerase II (the beta isoform), which does not cross-react with the 170 kDa form (the alpha isoform). Using this antibody, together with a polyclonal antibody specific for the 170 kDa isoform of topoisomerase II, we have examined the relationship between the sensitivity of a panel of human breast cancer cell lines to different classes of topoisomerase II inhibitors and cellular levels of the topoisomerase II alpha and beta proteins. We found that sensitivity to amsacrine showed a correlation with the level of expression of topoisomerase II alpha protein, and that sensitivity to etoposide showed a similar correlation with the level of expression of topoisomerase II beta protein. There was also a relationship between sensitivity of these cell lines to mitoxantrone and the cellular level of both isoforms of topoisomerase II. No relationship was found between the level of mRNA for topoisomerase II alpha or beta, and either sensitivity of breast cancer cell lines to topoisomerase II inhibitors or the level of topoisomerase II protein expression.