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首页> 外文期刊>Molecular and Cellular Biology >Functional identification of regulatory elements within the promoter region of platelet-derived growth factor 2.
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Functional identification of regulatory elements within the promoter region of platelet-derived growth factor 2.

机译：血小板衍生生长因子2启动子区域内调节元件的功能鉴定。

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Human platelet-derived growth factor (PDGF) is composed of two polypeptide chains, PDGF-1 and PDGF-2, the human homolog of the v-sis oncogene. Deregulation of PDGF-2 expression can confer a growth advantage to cells possessing the cognate receptor and, thus, may contribute to the malignant phenotype. We investigated the regulation of PDGF-2 mRNA expression during megakaryocytic differentiation of K562 cells. Induction by 12-O-tetradecanoylphorbol-13-acetate (TPA) led to a greater than 200-fold increase in PDGF-2 transcript levels in these cells. Induction was dependent on protein synthesis and was not enhanced by cycloheximide exposure. In our initial investigation of the PDGF-2 promoter, a minimal promoter region, which included sequences extending only 42 base pairs upstream of the TATA signal, was found to be as efficient as 4 kilobase pairs upstream of the TATA signal in driving expression of a reporter gene in uninduced K562 cells. We also functionally identified different regulatory sequence elements of the PDGF-2 promoter in TPA-induced K562 cells. One region acted as a transcriptional silencer, while another region was necessary for maximal activity of the promoter in megakaryoblasts. This region was shown to bind nuclear factors and was the target for trans-activation in normal and tumor cells. In one tumor cell line, which expressed high PDGF-2 mRNA levels, the presence of the positive regulatory region resulted in a 30-fold increase in promoter activity. However, the ability of the minimal PDGF-2 promoter to drive reporter gene expression in uninduced K562 cells and normal fibroblasts, which contained no detectable PDGF-2 transcripts, implies the existence of other negative control mechanisms beyond the regulation of promoter activity.
机译：人血小板衍生生长因子（PDGF）由两条多肽链PDGF-1和PDGF-2组成，这是v-sis癌基因的人类同源物。 PDGF-2表达的失调可以赋予具有同源受体的细胞以生长优势，因此可能有助于恶性表型。我们研究了在K562细胞巨核细胞分化过程中PDGF-2 mRNA表达的调节。 12-O-十四烷酰phorbol-13-乙酸盐（TPA）的诱导导致这些细胞中PDGF-2转录水平的增加幅度超过200倍。诱导依赖于蛋白质的合成，而环己酰亚胺的暴露并不能增强诱导作用。在我们对PDGF-2启动子的初步研究中，发现最小的启动子区域（包括仅在TATA信号上游延伸42个碱基对的序列）在驱动TGFβ-2启动子表达方面与TATA信号上游4个碱基对一样有效。未诱导的K562细胞中的报告基因。我们还在功能上确定了TPA诱导的K562细胞中PDGF-2启动子的不同调控序列元件。一个区域充当转录沉默子，而另一区域对于巨核细胞中启动子的最大活性是必需的。该区域显示出结合核因子，是正常细胞和肿瘤细胞中反式激活的靶标。在表达高PDGF-2 mRNA水平的一种肿瘤细胞系中，阳性调控区的存在导致启动子活性增加了30倍。然而，最小的PDGF-2启动子驱动未诱导的K562细胞和正常成纤维细胞中的报告基因表达的能力，其中不含可检测到的PDGF-2转录本，这暗示了除启动子活性调控之外的其他负控制机制的存在。

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