Samuel S K, Spencer V A, Bajno L, Sun J M, Holth L T, Oesterreich S, Davie J R
Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Cancer Res. 1998 Jul 15;58(14):3004-8.
Cisplatin is an antitumor drug that is used to treat several types of cancers. In this study, we analyzed the proteins that were cross-linked to DNA in situ in MCF-7 human breast cancer cells incubated with cisplatin. We show that cisplatin cross-links nuclear matrix proteins to DNA. In immunoblotting experiments, we found that nuclear matrix-associated transcription factors and cofactors (estrogen receptor, HET/SAF-B, hnRNP K, and histone deacetylase 1) were cross-linked to nuclear DNA. These transcription factors and cofactors have essential roles in the regulation of genes involved in the proliferation of breast cancer cells and in the organization and structure of chromatin. We applied a novel protocol to demonstrate that the nuclear matrix-bound transcription factors/cofactors were cross-linked to DNA fragments attached to the nuclear matrix. These results suggest that the cross-linking of nuclear matrix-associated transcription factors and cofactors to DNA may be one of the mechanisms by which cisplatin inhibits transcription and replication processes.
顺铂是一种用于治疗多种癌症的抗肿瘤药物。在本研究中，我们分析了在与顺铂孵育的MCF-7人乳腺癌细胞中与DNA原位交联的蛋白质。我们发现顺铂使核基质蛋白与DNA交联。在免疫印迹实验中，我们发现与核基质相关的转录因子和辅助因子（雌激素受体、HET/SAF-B、hnRNP K和组蛋白去乙酰化酶1）与核DNA交联。这些转录因子和辅助因子在参与乳腺癌细胞增殖的基因调控以及染色质的组织和结构中起着重要作用。我们应用了一种新方法来证明与核基质结合的转录因子/辅助因子与附着在核基质上的DNA片段交联。这些结果表明，与核基质相关的转录因子和辅助因子与DNA的交联可能是顺铂抑制转录和复制过程的机制之一。
