Jourdan M, De Vos J, Mechti N, Klein B
INSERM U475 and Unit for Cellular Therapy, CHU Montpellier, 34197 Montpellier, France.
Cell Death Differ. 2000 Dec;7(12):1244-52. doi: 10.1038/sj.cdd.4400758.
As survival regulation is a key process in multiple myeloma biology, we have studied the Bcl-2 family proteins that can be regulated by three myeloma cell survival factors: interleukin-6 (IL-6), interferon-alpha (IFN-alpha) and insulin-like growth factor (IGF-1). Eleven myeloma cell lines, whose survival and proliferation are dependent on addition of IL-6, variably expressed 10 anti-apoptotic or pro-apoptotic proteins of the Bcl-2-family. When myeloma cells from four cell lines were IL-6 starved and activated with IL-6 or IFN-alpha, we observed that only Mcl-1 expression was up-regulated with myeloma cell survival induction. Nor was obvious regulation of these 10 pro-apoptotic or anti-apoptotic proteins found with IGF-1, another potent myeloma cell survival factor. Our results indicate that the myeloma cell survival activity of IL-6 linked to Bcl-xL regulation cannot be generalized and emphasize that Mcl-1 is the main target of IL-6 and IFN-alpha stimulation. However, other changes in the activity of the Bcl-2 protein family or other apoptosis regulators must be identified to elucidate the IGF-1 action mechanism. Cell Death and Differentiation (2000) 7, 1244 - 1252.
由于生存调节是多发性骨髓瘤生物学中的关键过程，我们研究了可受三种骨髓瘤细胞生存因子调节的Bcl-2家族蛋白：白细胞介素-6（IL-6）、α干扰素（IFN-α）和胰岛素样生长因子（IGF-1）。11种骨髓瘤细胞系的生存和增殖依赖于添加IL-6，它们可变地表达Bcl-2家族的10种抗凋亡或促凋亡蛋白。当来自4种细胞系的骨髓瘤细胞处于IL-6饥饿状态并用IL-6或IFN-α激活时，我们观察到只有Mcl-1的表达随着骨髓瘤细胞生存诱导而上调。另一种有效的骨髓瘤细胞生存因子IGF-1也未对这10种促凋亡或抗凋亡蛋白产生明显调节作用。我们的结果表明，与Bcl-xL调节相关的IL-6的骨髓瘤细胞生存活性不能一概而论，并强调Mcl-1是IL-6和IFN-α刺激的主要靶点。然而，必须确定Bcl-2蛋白家族活性或其他凋亡调节因子的其他变化，以阐明IGF-1的作用机制。《细胞死亡与分化》（2000年）7卷，第1244 - 1252页 。
