端粒酶逆转录酶和P53在大鼠肝癌发生中的动态变化  

Dynamic changes of telomerase reverse transcriptase and P53 in the development of rat hepatocellular carcinoma

作　　者：陈颖[1] 孔庆忠[2,3] 

机构地区：[1]河南科技学院生命科技学院,河南省新乡市453003 [2]山东蓝金生物工程有限公司 [3]山东大学生命科学学院,山东省济南市250100

出　　处：《世界华人消化杂志》2009年第15期1493-1497,共5页World Chinese Journal of Digestology

摘　　要：目的:研究端粒酶逆转录酶(telomerase reverse transcriptase,TERT)和P53在大鼠肝癌发生过程的动态变化.方法:二乙基亚硝胺诱导大鼠肝细胞癌(hepatocellular carcinoma,HCC)的发生;免疫荧光方法检测TERT的表达变化;Western blot方法检测P53的表达;TRAP(telomeric repeatamplication protocol)方法检测端粒酶活性.结果:端粒酶与TERT在诱癌过程中呈逐渐升高的趋势,而P53在诱癌早期表达迅速升高后在诱癌后期表达急剧下降.定量分析表明炎症期P53的表达显著高于正常组织(3.53%±0.17%vs2.19%±0.15%,P=0.00),而在肝硬化期P53的表达量仅为0.98%±0.05%,至肝癌病变中几乎检测不到.与P53的表达变化趋势不同,端粒酶与TERT在炎症期有小幅升高,分别为34.47%±6.21%和6.43%±1.14%.肝硬化阶段端粒酶与TERT的表达迅速升高,至肝癌阶段达到高峰.统计学分析显示端粒酶与TERT的表达呈正相关(r=0.954,P=0.046),与P53的表达无相关性.结论:诱癌过程中逐渐升高的端粒酶活性和TERT的表达与P53的失活共同促进了肿瘤的发生,且三者均与肝癌的发生发展相一致可作为肝癌诊治的指标.AIM： To explore the expression of telomerase reverse transcriptase （TERT） and P53 in the development of rat hepatocellular carcinoma （HCC）. METHODS： A HCC model was induced by diethyl nitrosoamine （DENA）; telomerase activity was assayed using telomeric repeat amplication protocol （TRAP） method, whereas the expression of TERT and P53 was determined using immunofluorescence and Western blot, respectively. RESULTS： Compared with low expression level of TERT and telomerase activity, which were detected and maintained at a relative stable level in normal tissue and inflammatory lesion, the overxpression of telomerase and TERT were detected in hepatocirrhosis and HCC stage. However, the expression of P53 was significantly increased in inflammatory stage, and dramatically decreased in hepatocirrhosis stage, even undetectable in HCC stage. When quantified, in inflammation stage, the P53 expression level showed significant difference compared with control group （3.53% ±0.17% vs 2.19% ± 0.15%, P = 0.00）, whereas in hepatocirrhosis stage, the expression level of P53 was only 0.98%±0.05%. Contrary to the trend of P53 expression, the expression of telomerase, and TERT were very low in inflammation stage, which were 34.47% ± 6.21% and 6.43% ± 1.14%, respectively. But in hepatocirrhosis, telomerase activity, and TERT protein expression levels showed significant difference compared with control group and tended to culminate in HCC. Statistically analysis showed that telomerase was correlated with TERT （r = 0.954, P = 0.046）. As for P53, no relationship was found between P53 and telomerase and TERT. CONCLUSION： Accelerated telomerase, and TERT expression with P53 inactivation might synergistically contribute to carcinogenesis and be consistent with the progression of HCC, therefore the three factors may be useful tools in diagnosis and prognosis of HCC.

关 键 词：端粒酶逆转录酶 P53 端粒酶 肝细胞癌 端粒重复序列扩增法 

分 类 号：R735.7[医药卫生—肿瘤]