食管癌Egr-1基因表达及其与细胞凋亡的关系

RELATIONSHIP BETWEEN Egr-1 GENE EXPRESSION AND APOPTOSIS IN ESOPHAGEAL CARCINOMA

目的 研究早期生长反应基因 1(Egr 1基因 )和Bcl XL蛋白在人食管癌变过程中的表达及与细胞凋亡的关系。方法 应用原位杂交、免疫组织化学和TUNEL法检测 6 6例食管鳞状细胞癌及癌旁粘膜、上切缘粘膜中Egr 1mRNA和蛋白、凋亡相关蛋白Bcl XL和原位细胞凋亡。结果 食管上皮和食管癌细胞Egr 1基因原位杂交、Bcl XL蛋白免疫组化阳性物定位于细胞浆 ,Egr 1蛋白免疫组化阳性产物、TUNEL法阳性信号定位于细胞核。在食管癌变过程中 ,细胞凋亡发生率和凋亡指数逐渐升高 ;Egr 1mRNA及蛋白在食管粘膜上皮非典型增生中呈高表达。在癌组织 ,Egr 1阳性表达时凋亡指数显著高于其阴性表达 ;而Bcl XL阳性表达时凋亡指数显著低于其阴性表达。结论 细胞凋亡发生在食管癌变的全过程。Egr 1mRNA和蛋白在食管癌前病变呈高表达 ;Egr 1阳性鳞癌的凋亡指数显著升高 ;Egr 1有促进凋亡的作用。Egr 1的表达和细胞凋亡在食管癌变过程中可能有重要生物学意义。

? Objective To study the expression of early growth response gene-1 (Egr-1 gene) and Bcl-X/ Lprotein and their relationship with cell apoptosis in human esophageal carcinoma (EC).Method 66 cases of esophageal squamous cell carcinoma and their upper cut edge and paracancerous mucosa were analysed by using in situ hybridization (ISH), immunohistochemistry (IHC) and TUNEL method to detect Egr-1 mRNA, Egr-1 protein, apoptosis-related protein Bcl-X/ Land cell apoptosis. Result Egr-1 gene in situ hybridization and Bcl-X/ L positive products in immunocytochemical staining were located in the cytoplasm, while Egr-1 and TUNEL positive signals were located in the nuclei of the esophageal epitheliumand cancer cells. The cell apoptosis index (AI) and the frequency of apoptosis were increased gradually in the course of esophageal carcinogenesis, and the expression of Egr-1 mRNA and Egr-1 protein in atypicalhyperplasia was the highest among all specimens. The apoptosis index of Egr-1 positive cancer was much higher than that of Egr-1 negative ones, while that of Bcl-X/ Lpositive tissues was much lower than that of Bcl-X/ Lnegative ones. Conclusion Cell apoptosis was present during the whole process of malignant transformation of the esophagus. The expressions of Egr-1 mRNA and its protein were at high levels during the time of precancerous lesion. The apoptosis index was increased significantly in Egr-1 positive squamous cell carcinoma. These results indicat that Egr-1 might have the function of promoting cell apoptosis. Egr-1 expression and cell apoptosis may have an important biological significance in esophageal carcinogenesis. 〔