Overexpressing modified human TRβ1 suppresses the proliferation of breast cancer MDA-MB-468 cells.
Overexpressing modified human TRβ1 suppresses the proliferation of breast cancer MDA-MB-468 cells.
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过表达修饰的人 TRβ1 抑制乳腺癌 MDA-MB-468 细胞的增殖
DOI：
10.3892/ol.2018.8764
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发表时间：
2018-07
期刊：
影响因子：
2.9
通讯作者：
Zhao R
中科院分区：
文献类型：
--
作者：
Peng X;Zhang Y;Sun Y;Wang L;Song W;Li Q;Zhao R
大量研究表明甲状腺激素受体β1（TRβ1）具有抑癌作用。TR通过高度保守的DNA结合结构域（DBD）介导转录反应。先前鉴定了一种新的大鼠TRβ亚型（rTRβΔ），其中一个新的外显子N（108 bp）位于DBD内的外显子3和4之间;该外显子代表了rTRβΔ和rTRβ1之间的唯一差异。在体外，rTRβΔ表现出比rTRβ1更强的肿瘤抑制能力，进一步的分析显示大鼠和人DBD序列之间具有高度的保守性。本研究通过在野生型人TRβ1（wt-hTR β1）DBD的相应位置引入108 bp的序列，构建了人工修饰的人TR β 1（m-hTR β1）。电泳迁移率变动分析和转染实验证实m-hTRβ1是功能性的。过表达m-hTRβ1可抑制三碘甲腺原氨酸诱导的MDA-MB-468细胞增殖，其机制可能与上调Caspase-3和巴克基因表达，激活Caspase-3蛋白有关。此外，m-hTRβ1的促凋亡作用强于wt-hTRβ1。这些结果表明m-hTRβ1在MDA-MB-468细胞中可能具有抑癌作用。这些数据为乳腺癌的基因治疗提供了新的见解。
A number of studies have indicated that thyroid hormone receptor β1 (TRβ1) functions as a tumor suppressor. TRs mediate transcriptional responses through a highly conserved DNA-binding domain (DBD). A novel rat TRβ isoform (rTRβΔ) was previously identified, in which a novel exon, N (108 bp), is located between exons 3 and 4 within the DBD; this exon represents the only difference between rTRβΔ and rTRβ1. In vitro, rTRβΔ exhibits a stronger tumor-suppressive capacity than rTRβ1, and further analysis revealed a high level of conservation between the rat and human DBD sequences. In the present study, an artificially modified human TRβ1 (m-hTRβ1) was constructed via the introduction of the 108-bp sequence into the corresponding position of the wild-type human TRβ1 (wt-hTRβ1) DBD. An electrophoretic mobility shift assay and transfection experiments confirmed that m-hTRβ1 is functional. Overexpression of m-hTRβ1 inhibits the proliferation of MDA-MB-468 cells in the presence of triiodothyronine by promoting apoptosis, which may be associated with the upregulation of Caspase-3 and Bak gene expression and the activation of the Caspase-3 protein. In addition, the pro-apoptotic effect of m-hTRβ1 was stronger, compared with wt-hTRβ1. These results indicated that m-hTRβ1 may act as a tumor suppressor in MDA-MB-468 cells. These data provided a novel insight into gene therapy for breast cancer.
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DOI：
10.1016/j.bbrc.2014.01.012
发表时间：
2014-02-07
影响因子：
3.1
作者：
Ling, Yaqin;Shi, Xiangqun;Li, Qing
通讯作者：
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影响因子：
5.4
作者：
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影响因子：
6.6
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影响因子：
2.2
作者：
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Asif M
影响因子：
3.7
作者：
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