Role of thioredoxin reductase 1 in dysplastic transformation of human breast epithelial cells triggered by chronic oxidative stress.

Role of thioredoxin reductase 1 in dysplastic transformation of human breast epithelial cells triggered by chronic oxidative stress.
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硫氧还蛋白还原酶1在由慢性氧化应激触发的人乳腺上皮细胞的发育异常转化中的作用。

DOI:
10.1038/srep36860
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发表时间:
2016-11-15
期刊:
影响因子:
4.6
通讯作者:
Zeng H
Zeng H
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Dong C;Zhang L;Sun R;Liu J;Yin H;Li X;Zheng X;Zeng H

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硫氧还蛋白还原酶1(TrxR 1)是细胞内重要的氧化还原传感器和抗氧化酶。另一方面,TrxR 1的过表达与包括乳腺癌在内的各种肿瘤的发生密切相关,尽管详细的机制仍不清楚。在这里,我们研究了TrxR 1在慢性氧化应激诱导的人乳腺上皮细胞系MCF-10A异型增生转化中的作用。毫不奇怪,持续暴露于H2 O2显着增加MCF-10A细胞中TrxR 1的表达和活性。经8周H2 O2处理的异型增生转化的MCF-10A(MCF-10AT)细胞在致瘤性评价中表现出一定程度的恶性。此外,TrxR 1抑制剂ethaselen(BBSKE)可以部分逆转MCF-10AT和MCF-7细胞的一些恶性表型,包括上皮间质转化(EMT)。总的来说,我们的研究结果支持了TrxR 1在乳腺癌发病中的重要作用,BBSKE可能是一种有前途的乳腺癌治疗药物。
Thioredoxin reductase 1 (TrxR1) is a pivotal intracellular redox sensor and antioxidant enzyme. On the other hand, overexpression of TrxR1 is closely correlated with the initiation of various tumors including breast cancer, though the detailed mechanism remains unclear. Here we investigated the role of TrxR1 in dysplastic transformation of human breast epithelial cell line MCF-10A induced by chronic oxidative stress. Not surprisingly, sustained exposure to H2O2 significantly augmented the expression and activity of TrxR1 in MCF-10A cells. The dysplastically transformed MCF-10A (MCF-10AT) cells undergoing 8-week H2O2 treatment exhibited a certain degree of malignancy in tumorigenicity evaluation. Moreover, TrxR1 inhibitor ethaselen (BBSKE) could partially reverse some malignant phenotypes including epithelial to mesenchymal transition (EMT) of MCF-10AT as well as MCF-7 cells. Collectively, our results supported the considerable involvement of TrxR1 in the onset of breast cancer and BBSKE may be a promising agent against breast cancer.
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