Mitochondria-dependent and -independent mechanisms in tumour necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis are both regulated by interferon-γ in human breast tumour cells
Mitochondria-dependent and -independent mechanisms in tumour necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis are both regulated by interferon-γ in human breast tumour cells
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DOI：
10.1042/bj20020184
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发表时间：
2002-08-01
影响因子：
4.1
通讯作者：
López-Rivas, A
中科院分区：
文献类型：
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作者：
Ruiz-Ruiz, C;López-Rivas, A
肿瘤坏死因子相关凋亡诱导配体（TRAIL/APO-2L）在与死亡受体TRAIL-R1和TRAIL-R2结合后诱导多种肿瘤细胞凋亡。在这里，我们描述了敏化干扰素（IFN）-γ的TRAIL诱导的乳腺癌细胞系MCF-7和MDA-MB 231的凋亡。在这些细胞系中，IFN-γ促进TRAIL介导的半胱天冬酶-8活化、Bcl-2相互作用结构域死亡激动剂（Bid）降解、Bcl-2相关X蛋白（Bax）易位至线粒体、细胞色素c释放至细胞质和半胱天冬酶-9活化。在IFN-γ处理后未观察到TRAIL受体表达的变化。Bcl-2在MCF-7细胞中的过表达完全抑制IFN-γ诱导的对TRAIL介导的细胞死亡的敏化。有趣的是，TRAIL诱导的细胞凋亡也明显增强IFN-γ在caspase-3过表达的MCF-7细胞，在Bax易位到线粒体和细胞色素c释放到胞质溶胶的情况下。总之，我们的研究结果表明，IFN-γ促进TRAIL诱导的激活乳腺肿瘤细胞中的BRA调节以及BRA独立的凋亡途径。
Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL/APO-2L) induces apoptosis in a variety of tumour cells upon binding to death receptors TRAIL-R1 and TRAIL-R2. Here we describe the sensitization by interferon (IFN)-gamma to TRAIL-induced apoptosis in the breast tumour cell lines MCF-7 and MDA-MB231. IFN-gamma promoted TRAIL-mediated activation of caspase-8, Bcl-2 interacting domain death agonist (Bid) degradation, Bcl-2-associated X protein (Bax) translocation to mitochondria, cytochrome c release to the cytosol and activation of caspase-9 in these cell lines. No changes in the expression of TRAIL receptors were observed upon IFN-gamma treatment. Overexpression of Bcl-2 in MCF-7 cells completely inhibited IFN-gamma-induced sensitization to TRAIL-mediated cell death. Interestingly, TRAIL-induced apoptosis was also clearly enhanced by IFN-gamma in caspase-3-overexpressing MCF-7 cells, in the absence of Bax translocation to mitochondria and cytochrome c release to the cytosol. In summary, our results suggest that IFN-gamma facilitates TRAIL-induced activation of mitochondria-regulated as well as mitochondria-independent apoptotic pathways in breast tumour cells.