神经酰胺通过非p53途径诱导鼻咽癌细胞中p21^(WAF1)的表达  

Ceramide Induces p21^(WAF1)Expression Through p53-independent Pathway in Nasopharyngeal Carcinoma Cells

作　　者：朱孝峰[1] 张晓实[1] 李志铭[1] 姚毓奇 刘宗潮[1] 谢冰芬[1] 冯公侃[1] 曾益新[1] 

机构地区：[1]中山大学肿瘤防治中心肿瘤研究所,广东广州510060

出　　处：《中国肿瘤》2002年第4期237-239,共3页China Cancer

基　　金：教育部高等学校博士学科点基金(1998056912);国家自然科学基金(39900183);中山医科大学"211"工程重点学科基金(98069)

摘　　要：[目的]探讨第二信使神经酰胺信号传导诱导鼻咽癌细胞 p21WAF1表达的机理。[方法]Westernblot法检测 p53、p21、Jun、NFκB基因表达 ,试剂盒检测SAPK/JNK的活性。[结果]在鼻咽癌CNE2细胞中阿霉素能刺激 p53表达 ,不能上调p21WAF1 的表达 ,可见在CNE2细胞中p53为功能异常型。C2 - 神经酰胺处理CNE2细胞后 ,可见p53蛋白呈现下降趋势 ;而 p21WAF1 蛋白在处理4、16小时时 ,p21WAF1 表达明显增高 ,但36小时后 p21WAF1 恢复到基础水平。在6.25μmmol/L、12.5μmmol/L、25μmmol/L的C2_神经酰胺处理24小时后p21WAF1 上升 ,而50μmmol/L的C2_神经酰胺处理24小时后 ,p21WAF1 开始下降。C2_神经酰胺处理CNE2细胞2小时后 ,JNK的活性开始增加 ,6小时时保持激活状态 ,12小时时下降。c_Jun/AP_1蛋白在神经酰胺处理后3小时开始明显增高 ,持续到12小时 ,24小时下降至基础水平 ;C2_神经酰胺对CNE2细胞中NFκB蛋白表达没有明显的变化。[结论]C2_神经酰胺在鼻咽癌细胞CNE2中 ,通过p53非依赖性途经诱导p21WAF1 的表达。神经酰胺激活JNK ,从而激活AP_1因子 ,可能是其诱导 p21WAF1To investigate mechanism of p21WAF1 induction by ceramide in nasopharyngeal carcinoma cells. p53, p21, Jun expression was determined using western blot analysis. SAPK/JNK activity was examined with SAPK/JNK kit. The expression of protein p53 increased after treatment with adriamycin, whereas very low levels of p21WAF1 was observed in CNE2 cells and it was not changed upon drug treatment. It indicated that p53 status in CNE2 cells was dysfunctional. It did not upregulate p21WAF1 expression. The expression of p53 following treatment with ceramide for 3, 6, 12, 24h showed a tendence to decrease. Induction of p21WAF1 protein was observed when cells were treated with 50μmol/L ceramide for 4h, 16h, but not at 36h. The expression of p21WAF1 was upregulated following treatment with 6.25μmol/L, 12.5μmol/L, 25μmol/L ceramide for 24h, but the expression of p21WAF1 decreased to a basal level following 50μmol/L ceramide treatment for 24h. JNK activity increased 2h, 6h after ceramide treatment, but at 12h JNK activity decreased to a basal level. Ceramide upregulated c_Jun protein expression at 3h, remained elevated at 6h, whereas at 24h c_jun expression decreased. [Conclusion]Ceramide induced p21 expression through p53_independent pathway. Ceramide activates JNK, in turn activates Jun, AP_1 transcriptal factor. AP_1 may induce p21WAF1 expression.

关 键 词：神经酰胺 P53 P21^WAF1 鼻咽癌 表达 

分 类 号：R739.63[医药卫生—肿瘤]