Deregulated expression of interferon regulatory factor-1 in oncogene-transformed mouse fibroblasts.
Deregulated expression of interferon regulatory factor-1 in oncogene-transformed mouse fibroblasts.
复制标题
致癌基因转化的小鼠成纤维细胞中干扰素调节因子 1 的表达失调。
DOI：
10.1089/107999003322558773
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发表时间：
2003
期刊：
影响因子：
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通讯作者：
Friedman,RobertM
中科院分区：
文献类型：
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作者：
Contente,Sara;Attard,FrankA;Yeh,Tze-JouAnnie;Buchhagen,DorothyL;Friedman,RobertM
干扰素 (IFN) 调节因子-1 (IRF-1) 是一种转录因子，历史上与 I 型 IFN 激活和抗癌特性相关。我们研究了未转化和转化小鼠成纤维细胞中的 IRF-1 表达和 DNA 结合能力。 43 kDa 核 IRF-1 蛋白在原代小鼠胚胎成纤维细胞、未转化的 NIH 3T3 细胞和 andras 回复细胞的细胞周期中双相表达。 IRF-1 表达成为组成型 inras 转化的 NIH 3T3 细胞和癌基因组 fes、fos、her-2/neu、met、mos、raf、ortrk 转化的细胞，表明 IRF-1 表达失调可能与生长控制丧失有关。赖氨酰氧化酶（LO）是ras转化子中下调的arassuppressor，是IRF-1靶基因，但它不受转化子中存在的丰富IRF-1的刺激，而另一个IRF-1靶基因（iNOS）则被转录。来自正常 orras 转化细胞的 IRF-1 与 IFN-β 和 LO 启动子中的 IRF 元件结合。因此，转化体中的IRF-1可以结合但不反式激活LO启动子，并且IRF-1的存在不足以抑制转化。 LO表达可能影响IRF-1的表达调节：稳定转染LO cDNA产生的arasrevertant恢复了正常的双相IRF-1模式。正常细胞和转化细胞中也存在一种主要在细胞质中组成型表达的 46 kDa 蛋白，该蛋白与 43 kDa 核 IRF-1 具有免疫学同一性，但由于它不与 IRF 元件结合，因此其功能尚不清楚。
Interferon (IFN) regulatory factor-1 (IRF-1) is a transcription factor that has been historically associated with type I IFN activation and antioncogenic properties. We studied IRF-1 expression and DNA-binding capacity in nontransformed and transformed mouse fibroblasts. A 43-kDa nuclear IRF-1 protein was expressed biphasically during the cell cycle in primary mouse embryo fibroblasts, nontransformed NIH 3T3 cells, andrasrevertants. IRF-1 expression became constitutive inras-transformed NIH 3T3 cells and in cells transformed by oncogenesets,fes,fos,her-2/neu,met,mos,raf, ortrk, suggesting that deregulated IRF-1 expression may be associated with loss of growth control. Lysyl oxidase (LO), arassuppressor that is downregulated inrastransformants, is an IRF-1 target gene, but it is not stimulated by abundant IRF-1 present in transformants, while another IRF-1 target gene (iNOS) is transcribed. IRF-1 from either normal orras-transformed cells bound to IRF elements in the IFN-βand LO promoters. IRF-1 in transformants can, therefore, bind to but not transactivate the LO promoter, and the presence of IRF-1 is not sufficient to suppressrastransformation. LO expression may effect the regulated expression of IRF-1: arasrevertant, which was generated by stable transfection of LO cDNA, regained the normal biphasic IRF-1 pattern. A mainly cytoplasmic, constitutively expressed 46-kDa protein with immunologic identity to the 43-kDa nuclear IRF-1 was also present in normal and transformed cells, but as it did not bind to the IRF elements, its function is unclear.