间叶肉瘤端粒长度变化与相关调节蛋白表达的关系  

Correlation of telomere length and the expression of its regulating proteins in mesenchymal sarcomas

作　　者：迟英凯[1] 沈棋[1] 王教辰[1] 郑兴征[1] 侯琳[1] 张波[1] 

机构地区：[1]北京大学基础医学院病理学系

出　　处：《北京大学学报（医学版）》2008年第4期363-368,共6页Journal of Peking University:Health Sciences

基　　金：国家自然科学基金(30570691)资助~~

摘　　要：目的:观察间叶肉瘤端粒长度与P53、c-myc、TRF1、POT1、hTERT等相关调节蛋白的表达,探讨间叶肉瘤端粒长度变化规律及意义。方法:采用端粒荧光原位杂交和免疫组织化学方法检测了20例骨肉瘤、25例软骨肉瘤、19例横纹肌肉瘤、26例脂肪肉瘤中端粒长度、TRF1、POT1、hTERT,及P53、c-myc蛋白表达,并统计分析其与肿瘤类型及内在相关性。结果:骨肉瘤端粒长度短于软骨肉瘤、脂肪肉瘤(P<0.05),横纹肌肉瘤短于软骨肉瘤(P<0.05)。同时,端粒长度与不同组织学亚型软骨肉瘤和脂肪肉瘤相关,反映其恶性程度(P<0.05)。端粒长度变化与端粒结合蛋白POT1、TRF1表达具正相关性(P<0.05),而随着肿瘤端粒长度缩短端粒酶hTERT基因表达率增高(P<0.05),同时其P53蛋白核聚积及c-myc癌基因表达率也具有升高趋势。结论:端粒短缩普遍存在于间叶肉瘤,并可反映肉瘤的恶性程度;端粒短缩常与端粒结合蛋白TRF1、POT1的低表达及p53突变及c-myc和hTERT的激活有关,表明端粒短缩为间叶肉瘤发生和恶性演化的重要过程之一。Objective： To explore the significance in the change of telomere length in mesenchymal sarcomas, through analyzing telomere length and expression of its associated proteins, including TRF1, POT1, hTERT, P53 and c-myc. Methods： The telomere length in 20 cases of osteosarcomas, 25 of chondrosarcomas, 19 of rhabdomyosarcomas, 26 of liposarcomas was measured by telomere fluorescence in situ hybridization （Telo-FISH） , and the expression of TRF1, POT1, hTERT, p53 or c-myc was analyzed by immunohistochemistry, respectively. Results： The telomere length in osteosarcomas was significantly shorter than that of either chondrosarcomas or liposarcomas （P 〈 0. 05）. Similarly, the telomere length of rhabdomyosarcoma was shorter than that of chondrosarcoma （P 〈 0. 05）. Meanwhile, telomere shortening was positively correlated with down expression of telomere binding proteins TRF1 and POT1 （P 〈 0. 05）, but trends were detected more frequently in positive expression of hTERT （P 〈 0. 05 ） and in nuclear accumulation of P53 or expression of c-myc. With advancing in histological grading, telomere length was shortened markedly in chondrosarcomas, especially in liposarcomas （P 〈 0. 05）. Conclusion： The shortening of telomere could prevail in mesenchymal sarcoma and reflect the malignant potential. Telomere attrition usually correlated with down expression of POT1, TRF1 and with increased levels of hTERT, P53 and c-myc.

关 键 词：肉瘤 端粒 基因表达 

分 类 号：R730.2[医药卫生—肿瘤]