Response of human breast cancer cells to heat shock and chemotherapeutic drugs.
Response of human breast cancer cells to heat shock and chemotherapeutic drugs.
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发表时间：
1992-07
期刊：
影响因子：
11.2
通讯作者：
D. Ciocca;Suzanne A. W. Fuqua;S. Lock-Lim;David O. Toft;William J. Welch;William L. McGuire
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文献类型：
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作者：
D. Ciocca;Suzanne A. W. Fuqua;S. Lock-Lim;David O. Toft;William J. Welch;William L. McGuire
以前的研究表明，某些化疗药物是不太有效的肿瘤细胞时，细胞已预先暴露于高温。在本研究中，我们评估了热休克蛋白（hsp）表达的特定修饰是否与抗癌药物耐药性有关。在MCF-7/BK和MDA-MB-231乳腺癌细胞中，通过北方和狭缝印迹研究hsp 90、hsp 70和hsp 27的RNA水平，而通过二维凝胶电泳研究蛋白质。这些细胞对阿霉素，秋水仙碱，5-氟尿嘧啶，顺铂，放线菌素D，甲氨蝶呤的敏感性进行了测试，通过克隆形成试验。将这些技术应用于热休克前（对照）和热休克后的两种细胞系。研究表明，hsp 70和hsp 27水平升高与阿霉素耐药性有关。此外，磷酸化hsp 27亚型的存在也与阿霉素耐药相关。该研究表明，hsps的升高与多药耐药性无关。热休克不诱导P170糖蛋白mRNA的过度表达或对其他药物的耐药性。我们还发现，由热休克蛋白的过度表达所赋予的阿霉素保护水平低于在表达多药耐药表型的细胞（MDA-A1 R细胞）中获得的水平。在这些细胞中，热休克并没有赋予额外的阿霉素抗性，并且hsp 27磷酸化缺乏。我们的研究表明，特定的热休克蛋白与某些人乳腺癌细胞的阿霉素耐药性有关，而且这种机制似乎不依赖于多药耐药系统。
Previous studies have shown that certain chemotherapeutic drugs are less effective on tumor cells when cells have been previously exposed to hyperthermia. In the present study, we have evaluated whether specific modifications in heat shock protein (hsp) expression are associated with resistance to anticancer drugs. RNA levels for hsp90, hsp70, and hsp27 were studied by Northern and slot blots, while proteins were studied by two-dimensional gel electrophoresis, in MCF-7/BK and MDA-MB-231 breast cancer cells. The sensitivities of these cells to doxorubicin, colchicine, 5-fluorouracil, cisplatin, actinomycin D, and methotrexate were tested by clonogenic assays. These techniques were applied to both cell lines before (control) and after heat shock. The study revealed that elevated hsp70 and hsp27 levels were associated with doxorubicin resistance. In addition, the presence of phosphorylated hsp27 isoforms was also associated with doxorubicin resistance. The study showed that elevated hsps were not associated with multidrug resistance. Heat shock did not induce P170 glycoprotein mRNA overexpression or resistance to the other drugs tested. We also found that the level of doxorubicin protection conferred by the overexpression of hsp was lower than that obtained in cells expressing a multidrug resistance phenotype (MDA-A1R cells). In these cells, heat shock did not confer additional doxorubicin resistance and hsp27 phosphorylation was deficient. Our studies suggest that specific hsps are associated with doxorubicin resistance in certain human breast cancer cells and that this mechanism seems to be independent of the multidrug resistance system.