Gastroprotective peptide trefoil factor family 2 gene is activated by upstream stimulating factor but not by c-Myc in gastrointestinal cancer cells
Gastroprotective peptide trefoil factor family 2 gene is activated by upstream stimulating factor but not by c-Myc in gastrointestinal cancer cells
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DOI：
10.1136/gut.51.5.685
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发表时间：
2002-11-01
期刊：
影响因子：
24.5
通讯作者：
Lüscher, B
中科院分区：
文献类型：
--
作者：
Al-azzeh, E;Dittrich, O;Lüscher, B
背景：胃肠道粘膜损伤导致三叶因子家族肽TFF 1、TFF 2和TFF 3的急性上调。它们具有保护，愈合和肿瘤抑制功能。关于TFF基因表达的调控知之甚少。TFF基因的启动子均含有上游刺激因子（USF）和Myc/Max/Mad网络蛋白的结合位点（E box），目的：研究与这些E box结合的转录因子的性质和功能，了解它们在TFF基因表达中的作用。通过电迁移率变动分析和染色质免疫沉淀分析监测DNA结合。结果：TFF 2启动子可被USF转录因子特异性激活，而不被c-Myc激活。与三种TFF E盒相比，USF显示出与高亲和力Myc/Max结合位点相当的结合，而c-Myc显示出与TFF E盒较低的亲和力。相反，在强烈偏好USF与TFF 2 E盒特异性相互作用的细胞中观察到明显的结合差异，而Myc不高于背景。USF的外源性表达足以激活染色体TFF 2，并在较小程度上，TFF 1 gene.Conclusion：这些研究结果定义USF因子作为TFF 2基因的调节因子，并表明启动子特异性效应对于这种细胞保护肽的显著基因激活是重要的。
Background: Damage to the gastrointestinal mucosa results in the acute up-regulation of the trefoil factor family peptides TFF1, TFF2, and TFF3. They possess protective, healing, and tumour suppressive functions. Little is known about the regulation of TFF gene expression. The promoters of all three TFF genes contain binding sites (E box) for upstream stimulating factor (USF) and Myc/Max/Mad network proteins.Aims: To determine the nature and function of transcription factors that bind to these E boxes and to understand their role for TFF gene expression.Methods: TFF promoter activities were determined by reporter gene assays. DNA binding was monitored by electromobility shift assays and by chromatin immunoprecipitation analyses. Expression of endogenous TFF was determined by multiplex RT-PCR.Results: It was observed that the TFF2 promoter is specifically and efficiently activated by USF transcription factors but not by c-Myc. USF displayed comparable binding to a high affinity Myc/Max binding site compared with the three TFF E boxes, while c-Myc exhibited lower affinity to the TFF E boxes In contrast, pronounced binding differences were observed in cells with a strong preference for USF to interact specifically with the TFF2 E box, while Myc was not above background. Exogenous expression of USF was sufficient to activate the chromosomal TFF2 and to a lesser extent, the TFF1 gene.Conclusion: These findings define USF factors as regulators of the TFF2 gene and suggest that promoter specific effects are important for a pronounced gene activation of this cytoprotective peptide.