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首页> 外文期刊>Gene expression >Vascular endothelial growth factor (VEGF) is suppressed in WT1-transfected LNCaP cells.
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Vascular endothelial growth factor (VEGF) is suppressed in WT1-transfected LNCaP cells.

机译：WT1转染的LNCaP细胞中血管内皮生长因子（VEGF）被抑制。

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The Wilms' tumor suppressor gene product (WT1) regulates expression of growth control genes. Microarray analysis of gene expression profiles of hormone-treated LNCaP prostate cancer cell lines transfected with either wild-type WT1 or a zinc finger mutant form, DDS (R394W), revealed significantly altered patterns of expression. Validation studies using quantitative real-time PCR confirmed the differential expression of the tumor progression gene, vascular endothelial growth factor (VEGF). WT1-LNCaP cells had significantly reduced levels of VEGF mRNA when compared to vector control cells; in contrast, DDS-LNCaP cells showed elevated levels of VEGF transcripts. To address a functional role for WT1 overexpression, we investigated whether induction of VEGF expression, by the synthetic androgen R1881, would be disrupted in wild-type or mutant WT1-transfected LNCaP cells. Hormone treatment failed to elevate VEGF transcript levels above uninduced baseline levels in WT1-LNCaP cells, despite 48 h of treatment with 5 nM R1881. Consistent with our quantitative real-time PCR analysis, immunofluorescent staining of VEGF protein was reduced in WT1-LNCaP cells in both the presence and absence of R1881 treatment. Conversely, VEGF levels increased in vector control and DDS-LNCaP cells treated with 5 nM R1881. Not only do these studies point out the regulatory potential of WT1 for VEGF, but they also indicate an altered function for the mutant DDS isoform. Because VEGF is associated with neovascularization and promotion of metastasis in a variety of solid tumors including prostate cancer, a better understanding of the regulation of VEGF expression by transcription factors, such as WT1, is important for halting disease progression.
机译：威尔姆斯的肿瘤抑制基因产物（WT1）调节生长控制基因的表达。基因芯片分析了野生型WT1或锌指突变体形式DDS（R394W）转染的激素处理的LNCaP前列腺癌细胞系的基因表达谱，揭示了表达模式的显着改变。使用定量实时PCR进行的验证研究证实了肿瘤进展基因血管内皮生长因子（VEGF）的差异表达。与载体对照细胞相比，WT1-LNCaP细胞的VEGF mRNA水平显着降低。相反，DDS-LNCaP细胞显示VEGF转录物水平升高。为了解决WT1过表达的功能性作用，我们研究了在野生型或突变的WT1转染的LNCaP细胞中，合成雄激素R1881对VEGF表达的诱导是否会被破坏。尽管用5 nM R1881治疗了48小时，激素治疗仍未能使WT1-LNCaP细胞中的VEGF转录水平高于未诱导的基线水平。与我们的实时定量PCR分析一致，在有和没有R1881处理的情况下，WT1-LNCaP细胞中VEGF蛋白的免疫荧光染色均降低。相反，在用5 nM R1881处理的载体对照和DDS-LNCaP细胞中，VEGF水平升高。这些研究不仅指出了WT1对VEGF的调控潜力，而且还表明了突变DDS亚型的功能发生了改变。由于VEGF与包括前列腺癌在内的多种实体瘤中的新生血管形成和转移促进有关，因此更好地了解转录因子（例如WT1）对VEGF表达的调节对于中止疾病进展至关重要。

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