CA125在胃癌中的表达及c-Jun对CA125的调节机制

EXPRESSIONS OF CA125 IN PATIENTS WITH GASTRIC CANCER AND THE REGULATORY MACHENISM OF c- Jun TO CA125 IN GASTRIC CANCER CELLS

目的探讨糖类抗原CA125在胃癌中的表达差异,及在胃癌细胞中转录因子c-Jun对CA125的转录调节水平和可能的调控机制。方法 (1)选取胃癌患者(恶性组)、健康体检者(正常对照组)的血清为研究对象。检测血清CA125含量差异,检测胃癌患者血清CA125含量水平,并分析其与临床各参数间关系。(2)在胃癌细胞株823和803中,敲低c-Jun的表达水平,利用蛋白印迹法及实时定量PCR分别检测、分析CA125的蛋白和核酸水平变化。(3)敲低c-Jun的表达水平,利用荧光素酶报告基因实验检测CA125的转录活性。结果 CA125在胃癌组患者血清中的含量显著高于正常组(P<0.05),单因素结果分析显示胃癌患者外周血中CA125含量与肿瘤的浸润深度、远处转移、淋巴转移相关(P<0.05)。同时,体外实验提示,敲低胃癌细胞803、823中c-Jun的表达,发现CA125的mRNA水平也随即下调(P<0.05),但其蛋白水平并未受影响,而且通过荧光素酶报告基因实验发现,干扰c-Jun可显著抑制CA125基因启动子的转录活性,荧光素酶活性差异有统计学意义(P<0.05)。结论 CA125作为一种肿瘤标记物在胃癌中的表达存在差异,其差异、转移等因素可能受细胞内转录因子c-Jun的调节。

Objective To investigate the different levels of carbohydrate antigen 125 expression in patients with gastric cancer and explore the regulating mechanisms of CA125 by the transcription factor c - Jun. Methods First of all,we detect the different levels of carbohydrate antigen 125 in 86 cases patients with gastric cancer in trial group and 80 healthy persons in control group. And then analyzed the correlation of it with different clinicopathological pa- rameters in gastric cancer patients. Secondly, knock down the expression of c -Jun by siRNA, and detect the CA125 expression levels with Western blotting and Real time PCR in gastric cancer cells 803 and 823. At last, knocked down the c- Jun gene,and analyzed the regulating effect of c -Jun gene to CA125 transcription by Luciferase re- porter assays. Results The expression level of CA125 was significantly higher in trial group than in control （P 〈 0.05 ）and the CA125 expression levels were closely related with tumor invasions, distant metastasis and lymph node metastasis（P 〈0.05）. Moreover,as the expression of c -Jun was knocked down in 823 and 803, the CA125 mRNA levels was down -regulated, but its protein levels showed no changes. Luciferase reporter assays proved that the CA125 transcription was restrained by CA125_siRNA in cell lines（P 〈0.05 ）. Conclusion The expression level of CA125 is significantly higher in gastric cancer. The c - Jun - mediated transcriptional regulation is one of the key factors for CA125 expression. CA125 is as one of tumor marker shows different expression in gastric cancer cells and it may be regulated by intracelullar trancription factor c -Jun .