Thyroid hormone induces the expression of 4-1BB and activation of caspases in a thyroid hormone receptor-dependent manner
Thyroid hormone induces the expression of 4-1BB and activation of caspases in a thyroid hormone receptor-dependent manner
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DOI：
10.1046/j.1432-1033.2003.03686.x
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发表时间：
2003-07-01
期刊：
影响因子：
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通讯作者：
Yamada-Okabe, H
中科院分区：
文献类型：
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作者：
Yamada-Okabe, T;Satoh, Y;Yamada-Okabe, H
甲状腺激素对细胞增殖、生长和凋亡具有多种影响。为了更深入地了解甲状腺激素引起的分子动力学，对组成性过表达甲状腺激素受体（TR）的 HeLaTR 细胞中的基因表达进行了分析。使用寡核苷酸微阵列对 HeLaTR 细胞进行基因表达谱分析，得出 229 个基因，其表达被 T3 显着改变。在这些基因中，4-1BB 的表达被 T3 显着上调，4-1BB 已知会启动激活 NF-κB 的信号级联。尽管用 T3 处理 HeLaTR 细胞不会诱导 NF-kappaB 报告荧光素酶的表达，但即使在 4-1BB-配体存在的情况下，它也会增加 caspase 活性。在转染4-1BB cDNA的HeLaTR细胞中也观察到caspase活性的增加，并且4-1BB-Ligand进一步增加了过表达4-1BB的HeLaTR细胞的caspase活性。此外，仅表达真实 TR 的大鼠 FRTL 细胞中也出现了 4-1BB 的上调和 caspase 活性的增加。这些结果表明 4-1BB 的表达充当来自 T3 的信号介体以激活半胱天冬酶。
Thyroid hormone has various effects on cell proliferation, growth and apoptosis. To gain more insight into the molecular dynamics caused by thyroid hormone, gene expression in HeLaTR cells that constitutively overexpressed the thyroid hormone receptor (TR) was analyzed. Gene expression profiling of the HeLaTR cells with an oligonucleotide microarray yielded 229 genes whose expression was significantly altered by T3. Among these genes, the expression of 4-1BB, which is known to initiate a signal cascade activating NF-kappaB, was significantly up-regulated by T3. Although treatment of the HeLaTR cells with T3 did not induce expression of NF-kappaB reporter luciferase, even in the presence of the 4-1BB-Ligand, it increased the caspase activities. An increase in the caspase activities was also observed in the HeLaTR cells transfected with 4-1BB cDNA, and the 4-1BB-Ligand further increased the caspase activities of the HeLaTR cells overexpressing the 4-1BB. Furthermore, up-regulation of 4-1BB and an increase in caspase activities also occurred in the rat FRTL cells that expressed only authentic TR. These results demonstrate that the expression of 4-1BB serves as the mediator of signals from T3 to activate caspases.