Chen Quan, Ray Subrata, Hussein Mohamad A, Srkalovic Gordan, Almasan Alexandru
Department of Cancer Biology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH, USA.
Leuk Lymphoma. 2003 Jul;44(7):1209-14. doi: 10.1080/1042819031000068052.
Apo2 Ligand or Tumour Necrosis Factor (TNF)-Related Apoptosis-Inducing Ligand (Apo2L/TRAIL) is a member of the TNF gene superfamily that selectively induces apoptosis in tumor cells of diverse origins through engagement of death receptors. We have recently demonstrated that Type I interferons (IFN-alpha and beta) induce apoptosis in multiple myeloma (MM) cell lines and in plasma cells from MM patients. Moreover, Apo2L selectively induces apoptosis of patient MM tumor cells while sparing non-malignant cells. Apo2L induction is one of the earliest events following IFN administration in these cells. IFNs activate Caspases and the mitochondrial-dependent apoptotic pathway mediated by Apo2L production. Cell death induced by IFNs and Apo2L can be blocked by a dominant-negative Apo2L receptor, DRS, and is regulated by members of the Bcl-2 family of proteins. This review is focused on the apoptotic signaling pathways regulated by Apo2L and Bcl-2-family proteins and summarizes what is known about their clinical role.
Apo2配体或肿瘤坏死因子（TNF）相关凋亡诱导配体（Apo2L/TRAIL）是TNF基因超家族的成员，它通过死亡受体的结合选择性地诱导多种来源的肿瘤细胞凋亡。我们最近证明，I型干扰素（IFN-α和β）可诱导多发性骨髓瘤（MM）细胞系以及MM患者浆细胞凋亡。此外，Apo2L能选择性地诱导患者MM肿瘤细胞凋亡，同时使非恶性细胞免受影响。在这些细胞中，Apo2L的诱导是IFN给药后最早发生的事件之一。IFN激活半胱天冬酶以及由Apo2L产生介导的线粒体依赖性凋亡途径。IFN和Apo2L诱导的细胞死亡可被显性负性Apo2L受体DRS阻断，并受Bcl-2蛋白家族成员调节。本综述聚焦于由Apo2L和Bcl-2家族蛋白调节的凋亡信号通路，并总结了它们临床作用的已知情况。
