Inhibition of proliferation by 1-8U in interferon-α-responsive and non-responsive cell lines
Inhibition of proliferation by 1-8U in interferon-α-responsive and non-responsive cell lines
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DOI：
10.1007/s00018-003-3016-9
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发表时间：
2003-06-01
影响因子：
8
通讯作者：
Certa, U
中科院分区：
文献类型：
--
作者：
Brem, R;Oroszlan-Szovik, K;Certa, U
1-8基因家族的干扰素诱导蛋白介导同型黏附和抗增殖信号的转导。它们的诱导与抑制细胞生长有关，而在恶性转化和肿瘤发展过程中往往被抑制。RAS介导的小鼠肥大细胞转化与1-8U表达下调有关，干扰素-α治疗使1-8U诱导的肥大细胞增殖率恢复到正常水平。相反，在敏感的人黑色素瘤细胞中，干扰素-α的抗增殖反应伴随着1-8U的诱导。在这里，我们提供了直接证据表明，1-8U在人细胞系中的重组表达足以阻止细胞的增殖。基于对质膜和外体样结构的大量表达和亚细胞定位，我们提出了一个模型，能够解释1-8家族蛋白在肿瘤细胞和正常发育过程中的多向性功能。
Interferon (IFN)-inducible proteins of the 1-8 gene family mediate homotypic adhesion and transduction of antiproliferative signals. Their induction correlates with inhibition of cell growth while they are often repressed in the course of malignant transformation and tumor development. Ras-mediated transformation of mouse mast cells is associated with downregulation of 1-8U expression and interferon-alpha (IFN-alpha) treatment reverts the proliferation rate to normal levels together with induction of 1-8U. Conversely, the antiproliferative responses of IFN-alpha in sensitive human melanoma cells are accompanied by 1-8U induction. Here we provide direct evidence that recombinant expression of 1-8U in human cell lines is sufficient to block cell proliferation. Based on the abundant expression and subcellular localization to the plasma membrane and exosome-like structures, we propose a model capable of explaining the pleiotropic functions of 1-8 family proteins in tumor cells and during normal development.