CD30-induced up-regulation of the inhibitor of apoptosis genes cIAPl and cIAP2 in anaplastic large cell lymphoma cells
CD30-induced up-regulation of the inhibitor of apoptosis genes cIAPl and cIAP2 in anaplastic large cell lymphoma cells
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DOI：
10.1016/j.exphem.2004.01.003
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发表时间：
2004-04-01
影响因子：
2.6
通讯作者：
Müller, E
中科院分区：
文献类型：
--
作者：
Hübinger, G;Schneider, C;Müller, E
Objective.细胞因子受体CD 30的表达是间变性大细胞淋巴瘤（ALCL）的典型特征。CD 30诱导的效应对细胞活化和存活力具有很大影响。利用Karpas 299细胞，我们进行了差异显示逆转录聚合酶链反应（DDRT-PCR），以确定新的基因参与CD 30信号在ALCL。通过用固定的抗CD 30抗体处理诱导CD 30的活化。通过北方和Western印迹分析证实RNA和蛋白质在不同细胞系中的表达。应用流式细胞术（FACS）分析来检查细胞活力。核因子κ B（NF κ B）通路被阻断使用特定的信使。我们发现抗CD 30刺激的Karpas 299细胞中细胞凋亡抑制因子cIAP 1和cIAP 2的表达强烈增强。此外，我们发现，CD 30调节的cIAP 1和cIAP 2的表达是由NF κ B介导的。NF κ B、cIAP 1和cIAP 2的诱导与依托泊苷引起的凋亡性细胞死亡的部分保护相关。相应地，NF κ B通路的抑制不仅阻止了CD 30介导的普遍抗凋亡作用，甚至导致了CD 30诱导的细胞凋亡。最后，我们发现在其他几种ALCL细胞系和HD衍生细胞系HDLM-2中，cIAP 1和cIAP 2在CD 30刺激后表达增强。我们的研究结果表明，CD 30介导的保护凋亡是CD 30（+）细胞的共同特征。因此，CD 30诱导的信号传导可能对ALCL患者的临床结局产生显著影响。(C)2004年国际实验血液学学会。爱思唯尔公司出版
Objective. Expression of the cytokine receptor CD30 is a typical feature of anaplastic large cell lymphomas (ALCL). CD30-induced effects have a great impact on cell activation and viability.Materials and Methods. Using Karpas 299 cells, we performed differential display reverse transcriptase polymerase chain reaction (DDRT-PCR) to identify novel genes involved in CD30 signaling in ALCL. Activation of CD30 was induced by treatment with immobilized anti-CD30 antibody. RNA and protein expression were confirmed in different cell lines by Northern and Western blot analysis. Fluorescence-activated cell sorting (FACS) analysis was applied to examine cell viability. Nuclear factor kappaB (NFkappaB) pathways were blocked using a specific inhibitor.Results. We found strongly enhanced expression of the cellular inhibitor of apoptosis cIAP1 and cIAP2 in Karpas 299 cells stimulated with anti-CD30. Furthermore, we showed that CD30-regulated expression of cIAP1 and cIAP2 was mediated by NFkappaB. Induction of NFkappaB, cIAP1, and cIAP2 correlated with partial protection from apoptotic cell death caused by etoposide. Correspondingly, inhibition of the NFkappaB pathway not only prevented the prevalent antiapoptotic effects mediated by CD30, but even led to CD30-induced apoptosis. Finally, we found enhanced expression of cIAP1 and cIAP2 in several other ALCL cell lines and the HD-derived cell line HDLM-2 upon CD30 stimulation.Conclusions. Our results indicate that CD30-mediated protection from apoptosis is a common feature of CD30(+) cells. Therefore, CD30-induced signaling may have a significant impact on the clinical outcome of patients with ALCL. (C) 2004 International Society for Experimental Hematology. Published by Elsevier Inc.