摘要
食管癌研究的主要方向之一是找到较特异、而且变化频率较高的分子标志或影响肿瘤发生发展的关键基因。国内外在食管癌相关基因研究方面已做了大量工作,如在食管癌发现了p53、p16和MGMT的突变、c-myc和cyclin D扩增、Rb的杂合性缺失及其相应蛋白的表达异常。然而迄今为止,食管癌变的分子机制尚不清楚。因此,继续寻找食管癌发生发展的相关基因仍是食管癌研究的一个重要课题。
本研究采用mRNA差异显示技术比较了三例配对的食管癌/癌旁组织的基因表达情况,发现10个在食管癌中表达下调的基因,采用Northern blot、Dot blot、RT-PCR等技术确定了它们在食管癌中的异常表达频率。在这些获得的食管癌表达下调基因中,SPRR3、SPRR1、S100钙结合蛋白等是上皮细胞分化复合物的组成成分。我们同时发现催化这些蛋白形成分化复合物的酶TGM3在食管癌中也显著下调,提示上皮细胞分化复合物的形成障碍可能是食管癌变的一个重要事件。
本研究采用RH方法将在食管癌中表达下调的新基因C15orf6定位于15号染色体2区6带(15q26)。采用体外翻译系统获得了C15orf6的真核表达蛋白。制备了SPRR3以及C15orf6的多克隆抗体,从蛋白水平对SPRR3和C15orf6的表达进行了检测。结合免疫组化和GFP分析,发现C15orf6
Esophageal cancer is one of the most common malignancies of the digestive system in the world. The genetic changes in esophageal cancer have been reported as point mutations of p53 and p16, amplification of int-2, hst-1, cyclin D and EGFR, as well as loss of heterozygosity of Rb. But to date, the molecular basis underlying the transformation of normal esophageal epithelia to squamous carcinoma of the esophagus is not well understood. Identifying esophageal cancer related-genes is still an important project in exploring the mechanism of esophageal cancer.
In the present study, we have isolated and characterized 10 cDNA fragments down-regulated in esophageal cancer compared to matched adjacent normal mucosa using the mRNA differential display techniques. Of the cDNAs, such as SPRR3, SPRR1, S100 calcium-binding proteins are the compositions of the comified envelope (CE), an important barrier for the epithelial cells. We have found these genes were dramatically down-regulated in esophageal cancer. Interestingly, the enzyme TGM3 catalyzing the substrates to form the comified envelope was also found down-regulated in esophageal cancer. All the results suggested that the impediment of comified envelope forming was probably associated with the carcinogenesis of esophageal epithelia. To investigate the precise function of novel gene C15orf6 down-regulated in esophageal cancer, we defined the chromosome locus of C15orf6 by using
引文
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