人食管癌相关基因4在食管癌中的抑癌功能

Tumor-suppressing function of human esophageal cancer related gene 4 in esophageal squamous cell carcinoma

目的 探讨人食管癌相关基因4（ECRG4）在食管鳞状细胞癌（ESCC）中的抑癌功能及其机制.方法 利用DNA重组技术,构建ECRG4真核表达质粒pcDNA3.1-ECRG4,在ESCC细胞系EC9706细胞中转染表达ECRG4蛋白,检测细胞生长状态、细胞黏附、迁移、侵袭能力和裸鼠成瘤能力的改变.Western印迹检测ECRG4表达诱导P53和P21蛋白表达的变化.结果 ECRG4基因转染组裸鼠成瘤的最后体积和重量分别为（264±43）mm3和（0.39±0.09）g,对照组裸鼠分别为（464±128）mm3和（0.76±0.13）g,差异均有统计学意义（均P＜0.05）.ECRG4基因转染组肿瘤细胞与基质的黏附性、迁移和侵袭能力均低于对照组,但差异均无统计学意义（均P＞0.05）.ECRG4基因转染组P53和P21蛋白表达均高于对照组（100.00±3.87和35.71±2.36比16.6±1.92和1.09±0.11,均P＜0.05）.结论 ECRG4是ESCC的候选抑癌基因,ECRG4可能通过参与P53通路调控P21蛋白表达来发挥其抑癌功能.

Objective To investigate the tumor-suppressing function of human esophageal cancer related gene 4 （ECRG4） in esophageal squamous cell carcinoma （ESCC）. Methods The recombinant plasmid pcDNA3. 1-ECRG4 with ECRG4 open reading frame was constructed. The EC9706 cell was transfected with either pcDNA3. 1 or pcDNA3. 1-ECRG4. And the effects of ECRG4 on rumor cell were examined by in vivo assays of cell proliferation, adhesion, migration, invasion and tumor growth. The expression levels of P53 and P21 proteins were detected in EC9706 cell with transfection of ECRG4 gene by Western blotting. Results The final tumor volume and weight in ECRG4 transfection group were （264 ± 43）mm3 and（0. 39 ±0. 09）g, versus （464 ± 128）mm3 and （0. 76 ±0. 13）g in control group （both P 〈0. 05）.And the capacities of tumor cells adhesion, migration and invasion decreased in ECRG4 transfection group versus that in control group（all P 〉 0. 05）. Furthermore, the expression levels of P53 and P21 proteins were higher in ECRG4 transfection group than those in control group （100. 00 ± 3.87, 35.71 ± 2. 36 vs 16. 6 ±1.92, 1.09 ± 0. 11, both P 〈 0. 05）. Conclusion As a novel candidate tumor suppressor in ESCC,ECRG4 may induce the up-regulation of p21 protein through p53 pathway to inhibit tumor growth in ESCC.