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首页> 外文期刊>Zeitschrift fur Arznei- und Gewurzpflanzen >TCF 4 tumor suppressor: a molecular target in the prognosis of sporadic colorectal cancer in humans
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TCF 4 tumor suppressor: a molecular target in the prognosis of sporadic colorectal cancer in humans

机译：TCF 4肿瘤抑制剂：人类散发性结肠直肠癌预后的分子靶标

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Background A huge array of function is played by the Wnt/beta-catenin signaling pathway in development by balancing gene expression through the modulation of cell-specific DNA binding downstream effectors such as T-cell factor/lymphoid enhancer factor (TCF/LEF). The beta-catenin/TCF-4 complex is a central regulatory switch for differentiation and proliferation of intestinal cells (both normal and malignant). Thus, in the present study we evaluated each of 60 cases of sporadic adenocarcinoma, alongside adjoining and normal mucosa specimens of colorectum in humans, for mutation and expression analysis of the gene coding for TCF-4 protein. Methods DNA sequencing following PCR amplification and SSCP analysis (single strand conformation polymorphism) was employed to detect TCF-4 gene mutations in the case of exon 1. Quantitative real-time (qRT) PCR, immunohistochemistry (IHC), confocal microscopy and western blot analysis were used to detect TCF-4 gene/protein expression. Results Sequencing analysis confirmed 5/60 patients with a point mutation in exon 1 of the TCF-4 gene in tumor samples. mRNA expression using qRT-PCR showed approximately 83% decreased TCF-4 mRNA expression in tumor tissue and adjoining mucosa compared to normal mucosa. Similarly, a significant decrease in protein expression using IHC showed decreased TCF-4 protein expression in tumor tissue and adjoining mucosa compared to normal mucosa, which also corresponds to some important clinicopathological factors, including disease metastasis and tumor grade. Mutational alterations and downregulation of TCF-4 mRNA and hence decreased expression of TCF-4 protein in tumors suggest its involvement in the pathogenesis of CRC. Conclusions A remarkable decrease in TCF-4 mRNA and protein expression was detected in tumorous and adjoining tissues compared to normal mucosa. Hence the alterations in genomic architecture along with downregulation of TCF-4 mRNA and decreased expression of TCF-4 protein in tumors, which is in accordance with clinical features, suggest its involvement in the pathogenesis of CRC. Thus, deregulation and collaboration of TCF-4 with CRC could be a concrete and distinctive feature in the prognosis of the disease at an early stage of development.
机译：背景技术通过调节细胞特异性DNA结合下游效应（如T细胞因子/淋巴增强剂因子（TCF / LEF），通过平衡基因表达，通过平衡基因表达，通过平衡基因表达来发挥大量功能。 β-连环蛋白/ TCF-4复合物是肠细胞分化和增殖的中央调节开关（正常和恶性）。因此，在本研究中，我们评估了60例散发性腺癌，沿着人类的结肠蛋白的相邻和正常粘膜腺癌，用于TCF-4蛋白的基因突变和表达分析。方法采用PCR扩增和SSCP分析后的DNA测序（单链构象多态性）检测外显子1.定量实时（QRT）PCR，免疫组织化学（IHC），共聚焦显微镜和Western印迹中的TCF-4基因突变。分析用于检测TCF-4基因/蛋白表达。结果测序分析证实了5/60患者在肿瘤样品中TCF-4基因的外显子1中的点突变。使用QRT-PCR的mRNA表达显示肿瘤组织中的TCF-4 mRNA表达的约83％，与正常的粘膜相比邻近粘膜。类似地，与正常粘膜相比，使用IHC的蛋白质表达的显着降低显示肿瘤组织中的TCF-4蛋白表达和邻近粘膜，其对应于一些重要的临床病理因子，包括疾病转移和肿瘤等级。 TCF-4 mRNA的突变改变和下调，因此降低了TCF-4蛋白在肿瘤中的表达表明其参与CRC的发病机制。结论与正常粘膜相比，在肿瘤和邻接组织中检测到TCF-4 mRNA和蛋白表达的显着降低。因此，基因组架构的改变以及TCF-4 mRNA的下调和肿瘤中TCF-4蛋白的表达减少，符合临床特征，表明其参与CRC的发病机理。因此，具有CRC的Derculation和CRC的令人讨要和协作可能是在发育早期疾病的预后中的具体和独特的特征。

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