Thioltransferase overexpression increases resistance of MCF-7 cells to adriamycin

Thioltransferase overexpression increases resistance of MCF-7 cells to adriamycin
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DOI:
10.1016/s0891-5849(98)00247-0
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发表时间:
1999-03-01
影响因子:
7.4
通讯作者:
Wells, WW
Wells, WW
中科院分区:
医学1区
文献类型:
--
作者:
Meyer, EB;Wells, WW

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巯基转移酶是一种具有巯基-二硫化物氧化还原酶和脱氢抗坏血酸还原酶活性的小氧化还原蛋白,据报道,与阿霉素敏感的MCF-7 WT(MCF-7 WT)细胞相比,阿霉素耐药MCF-7人乳腺肿瘤细胞(MCF-7 ADR(R))中的表达水平更高。本研究检测了稳定转染人巯基转移酶cDNA的MCF-7 WT细胞的效果,以及随后在MCF-7 WT转染细胞中阿霉素细胞毒性的效果。所有过表达巯基转移酶活性的转染细胞系比未转染的MCF-7 WT细胞对阿霉素更具抗性,支持巯基转移酶表达增加与阿霉素抗性相关的假设。这种抗性不依赖于巯基转移酶催化脱氢抗坏血酸还原为抗坏血酸的能力,因为向培养基中加入抗坏血酸生成衍生物L-抗坏血酸-2-磷酸盐不会额外增加阿霉素抗性。(C)1999 Elsevier Science Inc.
Thioltransferase, a small redox protein with thiol-disulfide oxidoreductase and dehydroascorbate reductase activities, has been reported to be expressed at higher levels in Adriamycin-resistant MCF-7 human breast tumor cells (MCF-7 ADR(R)) when compared with Adriamycin sensitive MCF-7 WT (MCF-7 WT) cells. The present study examined the effects of stably transfecting MCF-7 WT cells with the cDNA for human thioltransferase and the effects of subsequent Adriamycin cytotoxicity in the MCF-7 WT transfected cells. All transfected cell lines overexpressing thioltransferase activity were more resistant to Adriamycin than untransfected MCF-7 WT cells, supporting the hypothesis that increases in thioltransferase expression are related to Adriamycin resistance. This resistance was independent of the ability of thioltransferase to catalyze reduction of dehydroascorbic acid to ascorbic acid, as the addition of an ascorbate generating derivative, L-ascorbic acid-2-phosphate, to the media did not additionally increase Adriamycin resistance. (C) 1999 Elsevier Science Inc.